Skip to main content

Innovative Approaches to Develop Prophylactic and Therapeutic Vaccines against HIV/AIDS

  • Chapter
Pharmaceutical Biotechnology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 655))

Abstract

The acquired immunodeficiency syndrome (AIDS) emerged in the human population in the summer of 1981. According to the latest United Nations estimates, worldwide over 33 million people are infected with human immunodeficiency virus (HIV) and the prevalence rates continue to rise globally. To control the alarming spread of HIV, an urgent need exists for developing a safe and effective vaccine that prevents individuals from becoming infected or progressing to disease. To be effective, an HIV/AIDS vaccine should induce broad and long-lasting humoral and cellular immune responses, at both mucosal and systemic level. However, the nature of protective immune responses remains largely elusive and this represents one of the major roadblocks preventing the development of an effective vaccine. Here we summarize our present understanding of the factors responsible for resistance to infection or control of progression to disease in human and monkey that may be relevant to vaccine development and briefly review recent approaches which are currently being tested in clinical trials. Finally, the rationale and the current status of novel strategies based on nonstructural HIV-1 proteins, such as Tat, Nef and Rev, used alone or in combination with modified structural HIV-1 Env proteins are discussed.

These authors have contributed equally to this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kresge KJ. Establishing accurate estimates of HIV incidence rates are critical to the success of prevention trials. International AIDS VAccine Initiative (IAVI) Report Vol. 11 (issue 3), 2007.

    Google Scholar 

  2. UNAIDs and WHO. AIDS Epidemic Update. Geneva, Switzerland: UNAIDS/WHO, 2006 (http:// data.unaids.org/pub/EpiReport/2006/03-Introduction-2006_EpiUpdate_eng.pdf) accessed 2007).

    Google Scholar 

  3. Walker BD, Rosenberg ES. Containing HIV after infection. Nat Med 2000; 6:1094–1095.

    Article  CAS  PubMed  Google Scholar 

  4. Rowland-Jones SL. Timeline: AIDS pathogenesis: what have two decades of HIV research taught us? Nat. Rev Immunol 2003; 3:343–348.

    Article  CAS  PubMed  Google Scholar 

  5. McMichael AJ. HIV vaccines. Annu Rev Immunol 2006; 24:227–255.

    Article  CAS  PubMed  Google Scholar 

  6. Spearman P. Current progress in the development of HIV vaccines. Curr Pharm Des 2006; 12:1147–1167.

    Article  CAS  PubMed  Google Scholar 

  7. Butler IF, Pandrea I, Marx PA et al. HIV genetic diversity: biological and public health consequences. Curr HIV Res 2007; 5:23–45.

    Article  CAS  PubMed  Google Scholar 

  8. Korber B, Gaschen B, Yusim K et al. Evolutionary and immunological implications of contemporary HIV-1 variation. Br Med Bull 2001; 58:19–42.

    Article  CAS  PubMed  Google Scholar 

  9. Wei X, Decker JM, Wang et al. Antibody neutralization and escape by HIV-1. Nature 2003; 422:307–312.

    Article  CAS  PubMed  Google Scholar 

  10. Asquith B, McLean AR. In vivo CD8+ T-cell control of immunodeficiency virus infection in humans and macaques. Proc Natl Acad Sci USA 2007; 104:6365–6370.

    Article  CAS  PubMed  Google Scholar 

  11. Vlasak J, Ruprecht RM. AIDs vaccine development and challenge viruses: getting real. AIDS 2006; 20:2135–2140.

    Article  PubMed  Google Scholar 

  12. Fackler OT, Alcover A, Schwartz O. Modulation of the imunological synapse: a key to HIV-1 pathogenesis. Nat Rev Immunol 2007; 7:310–317.

    Article  CAS  PubMed  Google Scholar 

  13. Goulder PJ, Watkins DI,. HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol 2004; 4:630–640.

    Article  CAS  PubMed  Google Scholar 

  14. Evans DT, Desrosiers RC. Immune evasion strategies of the primate lentiviruses. Immunol Rev 2001; 183:141–158.

    Article  CAS  PubMed  Google Scholar 

  15. Frahm N, Brander C. HIV viral diversity and escape from cellular immunity. Curr Infect Dis Rep 2007; 9:161–166.

    Article  PubMed  Google Scholar 

  16. McKay PF, Barouch DH, Schmitz JE et al. Global dysfunction of CD4 T-lymphocyte cytokine expression in simian-human immunodeficiency virus/SIV-infected monkeys is prevented by vaccination. J Virol 2003; 77:4695–4702.

    Article  CAS  PubMed  Google Scholar 

  17. Kulkarni PS, Butera ST, Duerr AC. Resistance to HIV-1 infection: lessons learned from studies of highly exposed persistently seronegative (HEPS) individuals. AIDs Rev 2003; 5:87–103.

    PubMed  Google Scholar 

  18. Goh WC, Markee J, Akridge RE et al. Protection against human immunodeficiency virus type 1 infection in persons with repeated exposure: evidence for T-cell immunity in the absence of inherited CCR5 coreceptor defects. J Infect Dis 1999; 179:548–557.

    Article  CAS  PubMed  Google Scholar 

  19. Hoffmann R. Gene expression patterns in human and mouse B-cell development. Curr Top Microbiol Immunol 2005; 294:19–29.

    Article  CAS  PubMed  Google Scholar 

  20. Fowke KR, Nagelkerke NJ, Kimani J et al. Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya. Lancet 1996; 348:1347–1351.

    Article  CAS  PubMed  Google Scholar 

  21. Kaul R, Rowland-Jones SL, Kimani J et al. Late seroconversion in HIV-resitant Nairobi prostitutes despite pre-existing HIV-specific CD8+ responses. J Clin Invest 2001; 107:341–349.

    Article  CAS  PubMed  Google Scholar 

  22. Kaul R, Rutherford J, Rowland-Jones SL et al. HIV-1 Env-specificdcytotoxic T-lymphocyte responses in exposed, uninfected Kenyan sex workers: a prospective analysis. AIDS 2004; 18:2087–2089.

    Article  PubMed  Google Scholar 

  23. Clerici M, Levin JM, Kessler HA et al. HIV-specific T-helper activity in seronegative health care workers exposed to contaminated blood. JAMA 1994; 271:42–46.

    Article  CAS  PubMed  Google Scholar 

  24. Pinto LA, Sullivan J, Berzofsky JA et al. ENV-specific cytotoxic T-lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. J Clin Invest 1995; 96:867–876.

    Article  CAS  PubMed  Google Scholar 

  25. Liu R, Paxton WA, Choe S et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996; 86:367–377.

    Article  CAS  PubMed  Google Scholar 

  26. Lopalco L, Pastori C, Barassi C et al. Heterogeneity in exposed uninfected individuals. J Biol Regul Homeost Agents 1997; 11:27–31.

    CAS  PubMed  Google Scholar 

  27. Schenal M, Lo CS, Fasano F et al. Distinct patterns of HIV-specific memory T-lymphocytes in HIV-exposed uninfected individuals and in HIV-infected patients. AIDS 2005; 19:635–661.

    Article  Google Scholar 

  28. Kaul R, Plummer FA, Kimani J et al. HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi. J Immunol 2000; 164:1602–1611.

    CAS  PubMed  Google Scholar 

  29. Furci L, Lopalco L, Loverro P et al. Noncytotoxic inhibition of HIV-1 infection by unstimulated CD8+ T-lymphocytes from HIV-exposed-uninfected individuals. AIDS 2002; 16:1003–1008.

    Article  CAS  PubMed  Google Scholar 

  30. Stranford SA, Skurnick J, Louria D et al. Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response. Proc Natl Acad Sci USA 1999; 96:1030–1035.

    Article  CAS  PubMed  Google Scholar 

  31. Alimonti JB, Koesters SA, Kimani J et al. CD4+ T-cell responses in HIV-exposed seronegative women are qualitatively distinct from those in HIV-infected women. J Infect Dis 2005; 191:20–24.

    Article  PubMed  Google Scholar 

  32. Montoya CJ, Velilla PA, Chougnet C et al. Increased IFN-gamma production by NK and CD3+/CD56+cell in sexually HIV-1-exposed but uninfected individuals. Clin Immunol 2006; 120:138–146.

    Article  CAS  PubMed  Google Scholar 

  33. Hirod T, Broliden K. Mucosal immune responses in the genital tract of HIV-1-exposed uninfected women. J Intern Med 2007; 262:44–58.

    Article  CAS  Google Scholar 

  34. Mazzoli S, Lopalco L, Salvi A et al. Human immunodeficiency virus (HIV)-specific IgA and HIV neutralizing activity in the serum of exposed seronegative partners of HIV-seropositive persons. J Infect Dis 1999; 180:871–875.

    Article  CAS  PubMed  Google Scholar 

  35. Kaul R, Trabattoni D, Bwayo JJ et al. HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers. AIDS 1999; 13:23–29.

    Article  CAS  PubMed  Google Scholar 

  36. Dorak MT, Tang J, Penman-Aguilar A et al. Transmission of HIV-1 and HLA-B allele-sharing within serodiscordant heterosexual Zambian couples. Lancet 2004; 363:2137–2139.

    Article  PubMed  Google Scholar 

  37. Wang CY, Cusack JC Jr, Liu R et al. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med 1999; 5:412–417.

    Article  PubMed  CAS  Google Scholar 

  38. Shearer GM, Pinto LA, Clerici M. Alloimmunization for immune-based therapy and vaccine design against HIV/AIDS. Immunol Today 1999;20:66–71.

    Article  CAS  PubMed  Google Scholar 

  39. Buchbinder SP, Katz MH, Hessol NA et al. Long-term HIV-1 infection without immunologic progression. AIDS 1994; 8:1123–1128.

    Article  CAS  PubMed  Google Scholar 

  40. Keet IP, Krol A, Klein MR et al. Characteristics of long-term asymptomatic infection with human immunodeficiency virus type 1 in men with normal and low CD4+ cell counts. J Infect Dis 1994; 169:1236–1243.

    CAS  PubMed  Google Scholar 

  41. Lefrere JJ, Morand-Joubert L, Mariotti M et al. Even individuals considered as long-term nonprogressors show biological signs of progression after 10 years of human immunodeficiency virus infection. Blood 1997; 90:1133–1140.

    CAS  PubMed  Google Scholar 

  42. Sheppard HW, Lang W, Ascher MS et al. The characterization of nonprogressors: long-term HIV-1 infection with stable CD4+ T-cell levels. AIDS 1993; 7:1159–1166.

    Article  CAS  PubMed  Google Scholar 

  43. Alexander L, Weiskopf E, Greenough TC et al. Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection. J Virol 2000; 74:4361–4376.

    Article  CAS  PubMed  Google Scholar 

  44. Deacon NJ, Tsykin A, Solomon A et al. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 1995; 270:988–991.

    Article  CAS  PubMed  Google Scholar 

  45. Hassaine G, Agostini I, Candotti D et al. Characterization of human immunodeficiency virus type 1 vif gene in long-term asymptomatic individuals. Virology 2000; 276:169–180.

    Article  CAS  PubMed  Google Scholar 

  46. Kirchhoff F, Greenough TC, Brettler DB et al. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med 1995; 332:228–232.

    Article  CAS  PubMed  Google Scholar 

  47. Lum JJ, Cohen OJ, Nie Z et al. Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. J Clin Invest 2003; 111:1547–1554.

    CAS  PubMed  Google Scholar 

  48. Wang B, Ge YC, Palasanthiran P et al. Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair: in vivo evolution of vpr quasispecies in blood and plasma. Virology 1996; 223:224–232.

    Article  CAS  PubMed  Google Scholar 

  49. Yamada T, Iwamoto A. Comparison of proviral accessory genes between long-term nonprogressors and progressors of human immunodeficiency virus type 1 infection. Arch Virol 2000; 145:1021–1027.

    Article  CAS  PubMed  Google Scholar 

  50. Daniel MD, Kirchhoff F, Czajak SC et al. Protective effects of a live attenuated SIV vaccine with a delection in the nef gene. Science 1992; 258:1938–1941.

    Article  CAS  PubMed  Google Scholar 

  51. Sernicola L, Corrias F, Koanga-Mogtomo ML et al. Long-lasting protection by live attenuated simian immunodeficiency virus in cynomolgus monkeys: no detection of reactivation after stimulation with a recall antigen. Virology 1999; 256:291–302.

    Article  CAS  PubMed  Google Scholar 

  52. Titti F, Sernicola L, Geraci A et al. Live attenuated simian immunodeficiency virus prevents super-infection by cloned SIVmac251 in cynomolgus monkeys. J Gen Virol 1997; 78:2529–2539.

    CAS  PubMed  Google Scholar 

  53. Learmont JC, Geczy AF, Mills J et al. Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort. N Engl J Med 1999; 340:1715–1722.

    Article  CAS  PubMed  Google Scholar 

  54. Baba TW, Liska V, Khimani AH et al. Live attenuated, multiply deleted simian immunodeficiency virus causes AIDs in infant and adult macaques. Nat Med 1999; 5:194–203.

    Article  CAS  PubMed  Google Scholar 

  55. Johnson RP, Lifson JD, Czajak SC et al. Highly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuation. J Virol 1999; 73:4952–4961.

    CAS  PubMed  Google Scholar 

  56. Koff WC, Johnson PR, Watkins DI et al. HIV vaccine design: insights from live attenuated SIV vaccines. Nat Immunol 2006; 7:19–23.

    Article  CAS  PubMed  Google Scholar 

  57. Cohen OJ, Vaccarezza M, Lam GK et al. Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors. J Clin Invest 1997; 100:1581–1589.

    Article  CAS  PubMed  Google Scholar 

  58. Gonzalez E, Kulkarni H, Bolivar H et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDs susceptibility. Science 2005; 307:1434–1440.

    Article  CAS  PubMed  Google Scholar 

  59. Kaslow RA, Carrington M, Apple R et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 1996; 2:405–411.

    Article  CAS  PubMed  Google Scholar 

  60. Kiepiela P, Ngumbela K, Thobakgale C et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 2007; 13:46–53.

    Article  CAS  PubMed  Google Scholar 

  61. Harari A, Cellerai C, Enders FB et al. Skewed association of polyfunctional antigen-specific CD8 T-cell populations with HLA-B genotype. Proc Natl Acad Sci USA 2007; 104:16233–16238.

    Article  CAS  PubMed  Google Scholar 

  62. Collins KL, Chen BK, Kalams SA et al. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T-lymphocytes. Nature 1998; 391:397–410.

    Article  CAS  PubMed  Google Scholar 

  63. Martin MP, Qi Y, Geo X et al. Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet 2007; 39:733–740.

    Article  CAS  PubMed  Google Scholar 

  64. Altfeld M, Goulder P. ‘Unleashed’ natural killers hinder HIV. Nat Genet 2007; 39:708–710.

    Article  CAS  PubMed  Google Scholar 

  65. Betts MR, Nason MC, West SM et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T-cells. Blood 2006; 107:4781–3789.

    Article  CAS  PubMed  Google Scholar 

  66. Pantaleo G, Harari A. Functional signatures in antiviral T-cell immunity for monitoring virus-associated diseases. Nat Rev Immunol 2006; 6:417–423.

    Article  CAS  PubMed  Google Scholar 

  67. Zimmerli SC, Harari A, Cellerai C et al. HIV-1-specific IFN-gamma/IL-2-secreting CD8 T-cells support CD4-independent proliferation of HIV-1-specific CD8 T-cells. Proc Natl Acad Sci USA 2005; 102:7239–7244.

    Article  CAS  PubMed  Google Scholar 

  68. Saez-Cirion A, Lacabaratz C, Lambotte O et al. HIV controllers exhibit potent CD8 T-cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T-lymphocyte activation phenotype. Proc Natl Acad Sci USA 2007; 104:6776–6781.

    Article  CAS  PubMed  Google Scholar 

  69. Arrode G, Finke JS, Zebroski H et al. CD8+ T-cells from most HIV-1-infected patients, even when challenged with mature dendritic cells, lack functional recal memory to HIV gag but not other viruses. Eur J Immunol 2005; 35:159–170.

    Article  CAS  PubMed  Google Scholar 

  70. Levy JA. The search for the CD8+ cell anti-HIV factor (CAF). Trends Immunol 2003; 24:628–632.

    Article  CAS  PubMed  Google Scholar 

  71. Cao J, McNevin J, Malhotra U et al. Evolution of CD8+ T-cell immunity and viral escape follwing acute HIV-1 infection J Immunol 2003; 171:3837–3846.

    CAS  PubMed  Google Scholar 

  72. Chun TW, Justement JS, Moir S et al. Suppression of HIV replication in the resting CD4+ T-cell reservoir by autologous CD8+ T-cells: implications for the development of therapeutic strategies. Proc Natl Acad Sci USA 2001; 98:253–258.

    Article  CAS  PubMed  Google Scholar 

  73. Norris PJ, Rosenberg ES. CD4(+) T-helper cells and the role they play in viral control. J Mol Med 2002; 80:397–405.

    Article  PubMed  Google Scholar 

  74. Kannanganat S, Ibegbu C, Chennareddi L et al. Multiple-cytokine-producing antiviral CD4 T-cells are functionally superior to single-cytokine-producing cells. J Virol 2007; 81:8468–8476.

    Article  CAS  PubMed  Google Scholar 

  75. Deeks SG, Walker BD. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 2007; 47:406–416.

    Article  CAS  Google Scholar 

  76. Dolan MJ, Kulkarni H, Camargo JF et al. CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms. Nat Immunol 2007; 8:1324–1336.

    Article  CAS  PubMed  Google Scholar 

  77. Fellay J, Shianna KV, Ge D et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007; 317:944–947.

    Article  CAS  PubMed  Google Scholar 

  78. Carotenuto P, Looij D, Keldermans L et al. Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection. AIDS 1998; 12:1591–1600.

    Article  CAS  PubMed  Google Scholar 

  79. Pilgrim AK, Pantaleo G, Cohen OJ et al. Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term-nonprogressive infection. J Infect Dis 1997; 176:924–932.

    Article  CAS  PubMed  Google Scholar 

  80. Bailey JR, Lassen KG, Yang HC et al. Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active anti-retroviral therapy. J Virol 2006; 80:4758–4770.

    Article  CAS  PubMed  Google Scholar 

  81. Humbert M, Antoni S, Brill B et al. Mimotopes selected with antibodies from HIV-1-neutralizing long-term nonprogressor plasma. Eur J Immunol 2007; 37:501–515.

    Article  CAS  PubMed  Google Scholar 

  82. Hirsch VM. What can natural infection of African monkeys with simian immunodeficiency virus tell us about the pathogenesis of AIDS? AIDS Rev 2004; 6:40–53.

    PubMed  Google Scholar 

  83. Kaur A, Grant RM, Means RE et al. Diverse host responses and outcomes following simian immunodeficiency virus SIVmac239 infection in sooty mangabeys and rhesus macaques. J Virol 1998; 72:9597–9611.

    CAS  PubMed  Google Scholar 

  84. Paiardini M, Cervasi B, Sumpter B et al. Perturbations of cell cycle control in T-cells contribute to the different outcomes of simian immunodeficiency virus infection in rhesus macaques and sooty mangabeys. J Virol 2006; 80:634–642.

    Article  CAS  PubMed  Google Scholar 

  85. Silvestri G. Naturally SIV-infected sooty mangabeys: are we closer to understanding why they do not develop AIDS? J Med Primatol 2005; 34:243–252.

    Article  CAS  PubMed  Google Scholar 

  86. Estes JD, Li Q, Reynolds MR et al. Premature induction of an immunosuppressive regulatory T-cell response during acute simian immunodeficiency virus infection. J Infect Dis 2006; 193:703–712.

    Article  CAS  PubMed  Google Scholar 

  87. Kornfeld C, Ploquin MJ, Pandrea I et al. Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest 2005; 115:1082–1091.

    CAS  PubMed  Google Scholar 

  88. Rouse BT, Sarangi PP, Suvas S. Regulatory T-cells in virus infections. Immunol Rev 2006; 212:272–286.

    Article  CAS  PubMed  Google Scholar 

  89. Gordon SN, Klatt NR, Bosinger SE et al. Severe Depletion of Mucosal CD4+ T-Cells in AIDS-Free Simian Immunodeficiency Virus-Infected Sooty Mangabeys. J Immunol 2007; 179:3026–3034.

    CAS  PubMed  Google Scholar 

  90. Milush JM, Reeves JD, Gordon SN et al. Virally induced CD4+ T-cell depletion is not sufficient to induce AIDS in a natural host. J Immunol 2007; 179:3047–3056.

    CAS  PubMed  Google Scholar 

  91. Pandrea IV, Gautam R, Ribeiro RM et al. Acute loss of intestinal CD4+ T-cells is not predictive of simian immunodeficiency virus virulence. J Immunol 2007; 179:3035–3046.

    CAS  PubMed  Google Scholar 

  92. Letvin NL, Huang Y, Chakrabarti BK et al. Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys. J Virol 2004; 78:7490–7497.

    Article  PubMed  CAS  Google Scholar 

  93. Letvin NL, Mascola JR, Sun Y et al. Preserved CD4+ central memory T-cells and survival in vaccinated SIV-challenged monkeys. Science 2006; 312:1530–1533.

    Article  CAS  PubMed  Google Scholar 

  94. Pantaleo G, Koup RA. Correlates of immune protection in HIV-1 infection: what we know, what we don’t know, what we should know. Nat Med 2004; 10:806–810.

    Article  CAS  PubMed  Google Scholar 

  95. Sun Y, Schmitz JE, Buzby AP et al. Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge. J Virol 2006; 80:10950–10956.

    Article  CAS  PubMed  Google Scholar 

  96. Humbert M, Dietrich U. The role of neutralizing antibodies in HIV infection. AIDS Rev 2006; 8:51–59.

    PubMed  Google Scholar 

  97. Johnston MI, Fauci AS. An HIV vaccine—evolving concepts. N Engl J Med 2007; 356:2073–2081.

    Article  CAS  PubMed  Google Scholar 

  98. Centlivre M, Sala M, Wain-Hobson S et al. In HIV-1 pathogenesis the die is cast during primary infection. AIDS 2007; 21:1–11.

    Article  PubMed  Google Scholar 

  99. Dandekar S. Pathogenesis of HIV in the gastrointestinal tract. Curr HIV/AIDS Rep 2007; 4:10–15.

    Article  PubMed  Google Scholar 

  100. Phogat S, Wyatt RT, Karlsson Hedestam GB. Inhibition of HIV-1 entry by antibodies: potential viral and cellular targets. J Intern Med 2007; 262:26–43.

    Article  CAS  PubMed  Google Scholar 

  101. Burton DR, Stanfield RL, Wilson IA. Antibody vs. HIV in a clash of svolutionary titans. Proc Natl Acad Sci USA 2005; 102:14943–14948.

    Article  CAS  PubMed  Google Scholar 

  102. Pantophlet R, Burton DR. GP120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol 2006; 24:739–769.

    Article  CAS  PubMed  Google Scholar 

  103. Zolla-Pazner S. Identifying epitopes of HIV-1 that induce protective antibodies. Nat Rev Immunol 2004; 4:199–210.

    Article  CAS  PubMed  Google Scholar 

  104. Ruprecht RM, Ferrantelli F, Kitabwalla M et al. Antibody protection: passive immunization of neonates against oral AIDS virus challenge. Vaccine 2003; 21:3370–3373.

    Article  CAS  PubMed  Google Scholar 

  105. Trkola A, Kuster H, Rusert P et al. Delay of HIV-1 rebound after cessation of anti-retroviral therapy through passive transfer of human neutralizing antibodies. Nat Med 2005; 11:615–622.

    Article  CAS  PubMed  Google Scholar 

  106. Haynes BF, Moody MA, Verkoczy L et al. Antibody polyspecificity and neutralization of HIV-1: a hypothesis. Hum Antibodies 2005; 14:59–67.

    PubMed  Google Scholar 

  107. Letvin NL. Progress and obstacles in the development of an AIDS vaccine. Nat Rev Immunol 2006; 6:930–939.

    Article  CAS  PubMed  Google Scholar 

  108. asa-Chapman MM, Hayman A, Newton P et al. Development of the antibody response in acute HIV-1 infection. AIDS 2004; 18:371–381.

    Article  Google Scholar 

  109. Yamamoto H, Kawada M, Takeda A et al. Post-infection immunodeficiency virus control by neutralizing antibodies. PLoS ONE 2007; 2:e540.

    Article  PubMed  CAS  Google Scholar 

  110. Holl V, Peressin M, Decoville T et al. Nonneutralizing antibodies are able to inhibit human immunodeficiency virus type 1 replication in macrophages and immature dendritic cells. J Virol 2006; 80:6177–6181.

    Article  CAS  PubMed  Google Scholar 

  111. de Arruda LB, Chikhlikar PR, August JT et al. DNA vaccine encoding human immunodeficiency virus-1 Gag, targeted to the major histocompatibility complex II compartment by lysosomal-associated membrane protein, elicits enhanced long-term memory response. Immunology 2004; 112:126–133.

    Article  PubMed  CAS  Google Scholar 

  112. Evans TG, Frey S, Israel H et al. Long-term memory B-cell responses in recipients of candidate human immunodeficiency virus type 1 vaccines. Vaccine 2004; 22:2626–2630.

    Article  CAS  PubMed  Google Scholar 

  113. Huber M, Trkola A. Humoral immunity to HIV-1: neutralization and beyond. J Intern Med 2007; 262:5–25.

    Article  CAS  PubMed  Google Scholar 

  114. Ahmad A, Menezes J. Antibody-dependent cellular cytotoxicity in HIV infections. FASEB J 1996; 10:258–266.

    CAS  PubMed  Google Scholar 

  115. Bjorling E, Broliden K, Bernardi D et al. Hyperimmune antisera against synthetic peptides representing the glycoprotein of human immunodeficiency virus type 2 can mediate neutralization and antibody-dependent cytotoxic activity. Proc Natl Acad Sci USA 1991; 88:6082–6086.

    Article  CAS  PubMed  Google Scholar 

  116. Brenner BG, Gryllis C, Wainberg MA. Role of antibody-dependent cellular cytotoxicity and lymphokine-activated killer cells in AIDS and related diseases. J Leukoc Biol 1991; 50:628–640.

    CAS  PubMed  Google Scholar 

  117. Broliden K, von GA, Persson C et al. Identification of cross-reactive antigenic target regions for HIV type 1-specific antibody-dependent cellular cytotoxicity. AIDS Res Hum Retroviruses 1996; 12:1699–1702.

    Article  CAS  PubMed  Google Scholar 

  118. Broliden PA, Ljunggren K, Hinkula J et al. A monoclonal antibody to human immunodeficiency virus type 1 which mediates cellular cytotoxicity and neutralization. J Virol 1990; 64:936–940.

    CAS  PubMed  Google Scholar 

  119. Ljunggren K, Broliden PA, Morfeldt-Manson L et al. IgG subclass response to HIV in relation to antibody-dependent cellular cytotoxicity at different clinical stages. Clin Exp Immunol 1988; 73:343–347.

    CAS  PubMed  Google Scholar 

  120. von Gegerfelt A, Nilsson C, Putkonen P et al. Broadly reactive HIV-2 and SIVmac specific antibody-dependent cellular cytotoxicity in immunized and infected cynomolgus monkeys. Vaccine 1994; 12:1203–1208.

    Article  Google Scholar 

  121. Gomez-Roman VR, Patterson LJ, Venzon D et al. Vaccine-elicited antibodies mediate antibody-dependent cellular cytotoxicity correlated with significantly reduced acute viremia in rhesus macaques challenged with SIVmac251. J Immunol 2005; 174:2185–2189.

    CAS  PubMed  Google Scholar 

  122. Hessell AJ, Hangartner L, Hunter M et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 2007; 449:101–104.

    Article  CAS  PubMed  Google Scholar 

  123. Emini EA, Koff WC. AIDS/HIV. Developing an AIDS vaccine: need, uncertainty, hope. Science 2004; 304:1913–1914.

    Article  CAS  PubMed  Google Scholar 

  124. Garber DA, Silvestri G, Feinberg MB. Prospects for an AIDS vaccine: three big questions, no easy answers. Lancet Infect Dis 2004;4:397–413.

    Article  CAS  PubMed  Google Scholar 

  125. Robinson HL, Amara RR. T-cell vaccines for microbial infections. Nat Med 2005; 11:S25–S32.

    Article  CAS  PubMed  Google Scholar 

  126. Douek DC, Kwong PD, Nabel GJ. The rational design of an AIDS vaccine. Cell 2006; 124:677–681.

    Article  CAS  PubMed  Google Scholar 

  127. Cocchi F, DeVico AL, Garzino-Demo A et al. Identification of RANTES, MIP-1 alpha and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T-cells. Science 1995; 270:1811–1815.

    Article  CAS  PubMed  Google Scholar 

  128. Walker CM, Steimer KS, Rosenthal KL et al. Identification of human immunodeficiency virus (HIV) envelope type-specific T-helper cells in an HIV-infected individual. J Clin Invest 1988; 82:2172–2175.

    Article  CAS  PubMed  Google Scholar 

  129. Goonetilleke N, Moore S, Dally L et al. Induction of multifunctional human immunodeficiency virus type 1 (HIV-1)-specific T-cells capable of proliferation in healthy subjects by using a prime-boost regimen of DNA-and modified vaccinia virus Ankara-vectored vaccines expressing HIV-1 Gag coupled to CD8+ T-cell epitopes. J Virol 2006; 80:4717–4728.

    Article  CAS  PubMed  Google Scholar 

  130. McMichael A, Hanke T. The quest for an AIDS vaccine: is the CD8+ T-cell approach feasible? Nat Rev Immunol 2002; 2:283–291.

    Article  CAS  PubMed  Google Scholar 

  131. Tobery TW, Dubey SA, Anderson K et al. A comparison of standard immunogenicity assays for monitoring HIV type 1 gag-specific T-cell responses in Ad5 HIV Type 1 gag vaccinated human subjects. AIDS Res Hum Retroviruses 2006; 22:1081–1090.

    Article  CAS  PubMed  Google Scholar 

  132. Addo MM, Yu XG, Rathod A et al. Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J Virol 2003; 77:2081–2092.

    Article  CAS  PubMed  Google Scholar 

  133. Betts MR, Ambrozak DR, Douek DC et al. Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: relationship to viral load in untreated HIV infection. J Virol 2001; 75:11983–11991.

    Article  CAS  PubMed  Google Scholar 

  134. Brander C, Frahm N, Walker BD. The challenges of host and viral diversity in HIV vaccine design. Curr Opin Immunol 2006; 18:430–437.

    Article  CAS  PubMed  Google Scholar 

  135. Sadagopal S, Amara RR, Montefiori DC et al. Signature for long-term vaccine-mediated control of a Simian and human immunodeficiency virus 89.6P challenge: stable low-breadth and low-frequency T-cell response capable of coproducing gamma interferon and interleukin-2. J Virol 2005; 79:3243–3253.

    Article  CAS  PubMed  Google Scholar 

  136. Dunham R, Pagliardini P, Gordon S et al. The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus. Blood 2006; 108:209–217.

    Article  CAS  PubMed  Google Scholar 

  137. Mattapallil JJ, Douek DC, Buckler-White A et al. Vaccination preserves CD4 memory T-cells during acute simian immunodeficiency virus challenge. J Exp Med 2006; 303:1533–1541.

    Article  CAS  Google Scholar 

  138. Casimiro DR, Chen L, Fu TM et al. Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene. J Virol 2003; 77:6305–6313.

    Article  CAS  PubMed  Google Scholar 

  139. Shiver JW, Fu TM, Chen L et al. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 2002; 415:331–335.

    Article  CAS  PubMed  Google Scholar 

  140. Casimiro DR, Wang F, Schleif WA et al. Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with dna and recombinant adenoviral vaccine vectors expressing Gag. J Virol 2005; 79:15547–15555.

    Article  CAS  PubMed  Google Scholar 

  141. McDermott AB, O’Connor DH, Fuenger S et al. Cytotoxic T-lymphocyte escape does not always explain the transient control of simian immunodeficiency virus SIVmac239 viremia in adenovirus-boosted and DNA-primed Mamu-A*01-positive rhesus macaques. J Virol 2005; 79:15556–15566.

    Article  CAS  PubMed  Google Scholar 

  142. HIV vaccine failure prompts Merck to halt trial. Nature 2007; 449:390.

    Google Scholar 

  143. Cohen J. AIDS research. Promising AIDS vaccine’s failure leaves field reeling. Science 2007; 318:28–29.

    Article  CAS  PubMed  Google Scholar 

  144. Betts MR, Exley B, Price DA et al. Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T-cell responses and their role in protection after HIV-1 infection. Proc Natl Acad Sci USA 2005; 102:4512–4517.

    Article  CAS  PubMed  Google Scholar 

  145. Staprans SI, Barry AP, Silvestri G et al. Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T-cell response to the SIV envelope protein. Proc Natl Acad Sci USA 2004; 101:13026–13031.

    Article  CAS  PubMed  Google Scholar 

  146. Graham BS. Infection with HIV-1. BMJ 1998; 317:1297–1301.

    CAS  PubMed  Google Scholar 

  147. Mascola JR, Snyder SW, Weislow OS et al. Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. J Infect Dis 1996; 173:340–348.

    CAS  PubMed  Google Scholar 

  148. Jeffs SA, Goriup S, Kebble B et al. Expression and characterisation of recombinant oligomeric envelope glycoproteins derived from primary isolates of HIV-1. Vaccine 2004; 22:1032–1046.

    Article  CAS  PubMed  Google Scholar 

  149. Stott EJ, Almond N, Kent K et al. Evaluation of a candidate human immunodeficiency virus type 1 (HIV-1) vaccine in macaques: effect of vaccination with HIV-1 gp120 on subsequent challenge with heterologous simian immunodeficiency virus-HIV-1 chimeric virus. J Gen Virol 1998; 79(Pt 3):423–432.

    CAS  PubMed  Google Scholar 

  150. Ferrantelli F, Cafaro A, Ensoli B. Nonstructural HIV proteins as targets for prophylactic or therapeutic vaccines. Curr Opin Biotechnol 2004; 15:543–556.

    Article  CAS  PubMed  Google Scholar 

  151. Flynn NM, Forthal DN, Harro CD et al. Placebo-controlled Phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 2005; 191:654–665.

    Article  PubMed  Google Scholar 

  152. Pitisuttithum P, Gilbert P, Gurwith M et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 2006; 194:1661–1671.

    Article  CAS  PubMed  Google Scholar 

  153. VaxGen 2007 (http://www.vaxgen.com).

    Google Scholar 

  154. Haynes BF, Montefiori DC. Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates. Expert Rev Vaccines 2006; 5:579–595.

    Article  CAS  PubMed  Google Scholar 

  155. Letvin NL, Barouch DH, Montefiori DC. Prospects for vaccine protection against HIV-1 infection and AIDS. Annu Rev Immunol 2002; 20:73–99.

    Article  CAS  PubMed  Google Scholar 

  156. Zolla-Pazner S, Gomy MK, Nyambi PN. The implications of antigenic diversity for vaccine development. Immunol Lett 1999; 66:159–164.

    Article  CAS  PubMed  Google Scholar 

  157. Hansen JE, Clausen H, Nielsen C et al. Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization. J Virol 1990; 64:2833–2840.

    CAS  PubMed  Google Scholar 

  158. Kwong PD, Doyle ML, Casper DJ et al. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature 2002; 420:678–682.

    Article  CAS  PubMed  Google Scholar 

  159. Reitter JN, Means RE, Desrosiers RC. A role for carbohydrates in immune evasion in AIDS. Nat Med 1998; 4:679–684.

    Article  CAS  PubMed  Google Scholar 

  160. Wyatt R, Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens and immunogens. Science 1998; 280:1884–1888.

    Article  CAS  PubMed  Google Scholar 

  161. Beddows S, Kirschner M, Campbell-Gardener L et al. Construction and characterization of soluble, cleaved and stabilized trimeric Env proteins based on HIV type 1 Env subtype A. AIDS Res Hum Retroviruses 2006; 22:569–579.

    Article  CAS  PubMed  Google Scholar 

  162. Kirschner M, Monrose V, Paluch M et al. The production of cleaved, trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein vaccine antigens and infectious pseudoviruses using linear polyethylenimine as a transfection reagent. Protein Expr Purif 2006; 48:61–68.

    Article  CAS  PubMed  Google Scholar 

  163. Richardson TM Jr, Stryjewski BL, Broder CC et al. Humoral response to oligomeric human immunodeficiency virus type 1 envelope protein. J Virol 1996; 70:753–762.

    CAS  PubMed  Google Scholar 

  164. Yang X, Wyatt R, Sodroski J. Improved elicitation of neutralizing antibodies against primary human immunodeficiency viruses by soluble stabilized envelope glycoprotein trimers. J Virol 2001; 75:1165–1171.

    Article  CAS  PubMed  Google Scholar 

  165. Buckner C, Gines LG, Saunders CJ et al. Priming B-cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV. Virology 2004; 320:167–180.

    Article  CAS  PubMed  Google Scholar 

  166. Cherpelis S, Shrivastava I, Gettie A et al. DNA vaccination with the human immunodeficiency virus type 1 SF162DeltaV2 envelope elicits immune responses that offer partial protection from simian/human immunodeficiency virus infection to CD8(+) T-cell-depleted rhesus macaques. J Virol 2001; 75:1547–1550.

    Article  CAS  PubMed  Google Scholar 

  167. Beddows S, Franti M, Dey AK et al. A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp 140, trimeric cleavage-defective gp 140 and monomeric gp 120. Virology 2007; 360:329–340.

    Article  CAS  PubMed  Google Scholar 

  168. Center RJ, Lebowitz J, Leapman RD et al. Promoting trimerization of soluble human immunodeficiency virus type 1 (HIV-1) Env through the use of HIV-1/simian immunodeficiency virus chimeras. J Virol 2004; 78:2265–2276.

    Article  CAS  PubMed  Google Scholar 

  169. Chakrabarti BK, Kong WP, Wu BY et al. Modifications of the human immunodeficiency virus envelope glycoprotein enhance immunogenicity for genetic immunization. J Virol 2002; 76:5357–5368.

    Article  CAS  PubMed  Google Scholar 

  170. Srivastava IK, Stamatatos L, Legg H et al. Purification and characterization of oligomeric envelope glycoprotein from a primary R5 subtype B human immunodeficiency virus. J Virol 2002; 76:2835–2847.

    Article  CAS  PubMed  Google Scholar 

  171. Yang X, Farzan M, Kolchinsky P et al. Modifications that stabilize human immunodeficiency virus envelope glycoprotein trimers in solution. J Virol 2000; 74:4746–4754.

    Article  CAS  PubMed  Google Scholar 

  172. Yang X, Lee J, Mahony EM et al. Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin. J Virol 2002; 76:4634–4642.

    Article  CAS  PubMed  Google Scholar 

  173. Zhang CW, Chishti Y, Hussey RE et al. Expression, purification and characterization of recombinant HIV gp140. The gp41 ectodomain of HIV or simian immunodeficiency virus is sufficient to maintain the retroviral envelope glycoprotein as a trimer. J Biol Chem 2001; 276:39577–39585.

    Article  CAS  PubMed  Google Scholar 

  174. Barnett SW, Lu S, Srivastava I et al. The ability of an oligomeric human immunodeficiency virus type 1 (HIV-1) envelope antigen to elicit neutralizing antibodies against primary HIV-1 isolates is improved following partial deletion of the second hypervariable region. J Virol 2001; 75:5526–5540.

    Article  CAS  PubMed  Google Scholar 

  175. Bower JF, Yang X, Sodroski J et al. Elicitation of neutralizing antibodies with DNA vaccines expressing soluble stabilized human immunodeficiency virus type 1 envelope glycoprotein trimers conjugated to C3d. J Virol 2004; 78:4710–4719.

    Article  CAS  PubMed  Google Scholar 

  176. Kim M, Qiao ZS, Montefiori DC et al. Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies. AIDS Res Hum Retroviruses 2005; 21:58–67.

    Article  CAS  PubMed  Google Scholar 

  177. VanCott TC, Mascola JR, Kaminski RW et al. Antibodies with specificity to native gp120 and neutralization activity against primary human immunodeficiency virus type 1 isolates elicited by immunization with oligometric gp160. J Virol 1997; 71:4319–4330.

    CAS  PubMed  Google Scholar 

  178. Binley JM, Sanders RW, Clas B et al. A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol 2000; 74:627–643.

    Article  CAS  PubMed  Google Scholar 

  179. Sanders RW, Vesanen M, Schuelke N et al. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol 2002; 76:8875–8889.

    Article  CAS  PubMed  Google Scholar 

  180. Schulke N, Vesanen MS, Sanders RW et al. Oligomeric and conformational properties of a proteolytically mature, disulfide-stabilized human immunodeficiency virus type 1 gp140 envelope glycoprotein. J Virol 2002; 76:7760–7776.

    Article  CAS  PubMed  Google Scholar 

  181. Beddows S, Schulke N, Kirschner M et al. Evaluating the immunogenicity of a disulfide-stabilized, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol 2005; 79:8812–8827.

    Article  CAS  PubMed  Google Scholar 

  182. Billington J, Hickling TP, Munro GH et al. Stability of a receptor-binding active human immunodeficiency virus type 1 recombinant gp140 trimer conferred by intermonomer disulfide bonding of the V3 loop: differential effects of protein disulfide isomerase on CD4 and coreceptor binding. J Virol 2007; 81:4604–4614.

    Article  CAS  PubMed  Google Scholar 

  183. Dey AK, David KB, Klasse PJ et al. Specific amino acids in the N-terminus of the gp41 ectodomain contribute to the stabilization of a soluble, cleaved gp140 envelope glycoprotein from human immunodeficiency virus type 1. Virology 2007; 360:199–208.

    Article  CAS  PubMed  Google Scholar 

  184. Forsell MN, Li Y, Sundback M et al. Biochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by semliki forest virus. J Virol 2005; 79:10902–10914.

    Article  CAS  PubMed  Google Scholar 

  185. Yang X, Kurteva S, Ren X et al. Subunit stoichiometry of human immunodeficiency virus type 1 envelope glycoprotein trimers during virus entry into host cells. J Virol 2006; 80:4388–4395.

    Article  CAS  PubMed  Google Scholar 

  186. Barnett SW, Srivastava IK, Ulmer JB et al. Development of V2-deleted trimeric envelope vaccine candidates from human immunodeficiency virus type 1 (HIV-1) subtypes B and C. Microbes Infect 2005; 7:1386–1391.

    Article  CAS  PubMed  Google Scholar 

  187. Srivastava IK, Stamatatos L, Kan E et al. Purification, characterization and immunogenicity of a soluble trimeric envelope protein containing a partial deletion of the V2 loop derived from SF162, an R5-tropic human immunodeficiency virus type 1 isolate. J Virol 2003; 77:11244–11259.

    Article  CAS  PubMed  Google Scholar 

  188. Srivastava IK, VanDorsten K, Vojtech L et al. Changes in the immunogenic properties of soluble gp140 human immunodeficiency virus envelope constructs upon partial deletion of the second hypervariable region. J Virol 2003; 77:2310–2320.

    Article  CAS  PubMed  Google Scholar 

  189. Devico A, Silver A, Thronton AM et al. Covalently crosslinked complexes of human immunodeficiency virus type 1 (HIV-1) gp120 and CD4 receptor elicit a neutralizing immune response that includes antibodies selective for primary virus isolates. Virology 1996; 218:258–263.

    Article  CAS  PubMed  Google Scholar 

  190. Fouts T, Godfrey K, Bobb K et al. Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques. Proc Natl Acad Sci USA 2002; 99:11842–11847.

    Article  CAS  PubMed  Google Scholar 

  191. Wahren B, Liu M. Therapeutic vaccination against HIV. Expert Rev Vaccines 2004; 3:S179–S188.

    Article  CAS  PubMed  Google Scholar 

  192. Tavel JA, Martin JE, Kelly GG et al. Safety and immunogenicity of a Gag-Pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1-seronegative subjects. J Acquir Immune Defic Syndr 2007; 44:601–605.

    Article  CAS  PubMed  Google Scholar 

  193. Barouch DH, Kunstman J, Kuroda MJ et al. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T-lymphocytes. Nature 2002; 415:335–339.

    Article  CAS  PubMed  Google Scholar 

  194. Barouch DH, Kunstman J, Glowczwskie J et al. Viral escape from dominant simian immunodeficiency virus epitope-specific cytotoxic T-lymphocytes in DNA-vaccinated rhesus monkeys. J Virol 2003; 77:7367–7375.

    Article  CAS  PubMed  Google Scholar 

  195. Buttò S, Fiorelli V, Tripiciano A et al. Sequence conservation and antibody cross-recognition of clade B human immunodeficiency virus (HIV) type 1 Tat protein in HIV-1-infected Italians, Ugandans and South Africans. J Infect Dis 2003; 188:1171–1180.

    Article  PubMed  Google Scholar 

  196. Robert-Guroff M. HIV regulatory and accessory proteins: new targets for vaccine development. DNA Cell Biol 2002; 21:597–598.

    Article  CAS  PubMed  Google Scholar 

  197. Wu Y, Marsh JW. Selective transcription and modulation of resting T-cell activity by preintegrated HIV DNA. Science 2001; 293:1503–1506.

    Article  CAS  PubMed  Google Scholar 

  198. Addo MM, Altfeld M, Rosenberg ES et al. The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T-lymphocytes derived from HIV-1-infected individuals. Proc Natl Acad Sci USA 2001; 98:1781–1786.

    Article  CAS  PubMed  Google Scholar 

  199. Addo MM, Yu XG, Rosenberg ES et al. Cytotoxic T-lymphocyte (CTL) responses directed against regulatory and accessory proteins in HIV-1 infection. DNA Cell Biol 2002; 21:671–678.

    Article  CAS  PubMed  Google Scholar 

  200. Liu Z, Xiao Y, Chen YH. Epitope-vaccine strategy against HIV-1: today and tomorrow. Immunobiology 2003; 208:423–428.

    Article  CAS  PubMed  Google Scholar 

  201. Yu XG, Lichterfeld M, Addo MM et al. Regulatory and accessory HIV-1 proteins: potential targets for HIV-1 vaccines? Curr Med Chem 2005; 12:741–747.

    Article  CAS  PubMed  Google Scholar 

  202. Bobbitt KR, Addo MM, Altfeld M et al. Rev activity determines sensitivity of HIV-1-infected primary T-cells to CTL killing. Immunity 2003; 18:289–299.

    Article  CAS  PubMed  Google Scholar 

  203. Li L, Li HS, Pauza CD et al. Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions. Cell Res 2005; 15:923–934.

    Article  CAS  PubMed  Google Scholar 

  204. Seelamgari A, Maddukuri A, Berro R et al. Role of viral regulatory and accessory proteins in HIV-1 replication. Front Biosci 2004; 9:2388–2413.

    Article  CAS  PubMed  Google Scholar 

  205. Joseph AM, Kumar M, Mitra D. Nef: “necessary and enforcing factor” in HIV infection. Curr HIV Res 2005; 3:87–94.

    Article  CAS  PubMed  Google Scholar 

  206. Caputo A, Gavioli R, Ensoli B. Recent advances in the development of HIV-1 Tat-based vaccines. Curr HIV Res 2004; 2:357–376.

    Article  CAS  PubMed  Google Scholar 

  207. Huang L, Bosch I, Hofmann W et al. Tat protein induces human immunodeficiency virus type 1 (HIV-1) coreceptors and promotes infection with both macrophage-tropic and T-lymphotropic HIV-1 strains. J Virol 1998; 72:8952–8960.

    CAS  PubMed  Google Scholar 

  208. Secchiero P, Zella D, Capitani S et al. Extracellular HIV-1 tat protein up-regulates the expression of surface CXC-chemokine receptor 4 in resting CD4+ T-cells. J Immunol 1999; 162:2427–2431.

    CAS  PubMed  Google Scholar 

  209. Fanales-Belasio E, Moretti S, Nappi F et al. Native HIV-1 Tat protein targets monocyte-derived dendritic cells and enhances their maturation, function and antigen-specific T-cell responses. J Immunol 2002; 168:197–206.

    CAS  PubMed  Google Scholar 

  210. Kim DT, Mitchell DJ, Brockstedt DG et al. Introduction of soluble proteins into the MHC class I pathway by conjugation to an HIV tat peptide. J Immunol 1997; 159:1666–1668.

    CAS  PubMed  Google Scholar 

  211. Moy P, Daikh Y, Pepinsky B et al. Tat-mediated protein delivery can facilitate MHC class I presentation of antigens. Mol Biotechnol 1996; 6:105–113.

    Article  CAS  PubMed  Google Scholar 

  212. Gavioli R, Gallerani E, Fortini C et al. HIV-1 tat protein modulates the generation of cytotoxic T-cell epitopes by modifying proteasome composition and enzymatic activity. J Immunol 2004; 173:3838–3843.

    CAS  PubMed  Google Scholar 

  213. Remoli AL, Marsili G, Perrotti E et al. Intracellular HIV-1 Tat protein represses constitutive LMP2 transcription increasing proteasome activity by interfering with the binding of IRF-1 to STAT1. Biochem J 2006; 396:371–380.

    Article  CAS  PubMed  Google Scholar 

  214. Allen TM, Altfeld M, Yu XG et al. Selection, transmission and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection. J Virol 2004; 78:7069–7078.

    Article  CAS  PubMed  Google Scholar 

  215. Yokomaku Y, Miura H, Tomiyama H et al. Impaired processing and presentation of cytotoxic-T-lymphocyte (CTL) epitopes are major escape mechanisms from CTL immune pressure in human immunodeficiency virus type 1 infection. J Virol 2004; 78:1324–1332.

    Article  CAS  PubMed  Google Scholar 

  216. Gavioli R, Cellini S, Castaldello A et al. The Tat protein broadens T-cell responses directed to the HIV-1 antigens Gag and Env: Implications for the design of new vaccination strategies against AIDS. Vaccine 2008; 26:727–737.

    Article  CAS  PubMed  Google Scholar 

  217. Gruters RA, van Baalen CA, Osterhaus AD. The advantage of early recognition of HIV-infected cells by cytotoxic T-lymphocytes. Vaccine 2002; 20:2011–2015.

    Article  CAS  PubMed  Google Scholar 

  218. Allen TM, O’Connor DH, Jing P et al. Tat-specific cytotoxic T-lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature 2000; 407:386–390.

    Article  CAS  PubMed  Google Scholar 

  219. Loffredo JT, Rakasz EG, Giraldo JP et al. Tat(28–35)SL8-specific CD8+ T-lymphocytes are more effective than Gag(181–189)CM9-specific CD8+ T-lymphocytes at suppressing simian immunodeficiency virus replication in a functional in vitro assay. J Virol 2005; 79:14986–14991.

    Article  CAS  PubMed  Google Scholar 

  220. O’Connor DH, Allen TM, Vogel TU et al. Acute phase cytotoxic T-lymphocyte escape is a hallmark of simian immunodeficiency virus infection. Nat Med 2002; 8:493–499.

    Article  PubMed  CAS  Google Scholar 

  221. O’Connor DH, Mothe BR, Weinfurter JT et al. Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses. J Virol 2003; 77:9029–9040.

    Article  PubMed  CAS  Google Scholar 

  222. van Baalen CA, Pontesilli O, Huisman RC et al. Human immunodeficiency virus type 1 Rev-and Tat-specific cytotoxic T-lymphocyte frequencies inversely correlate with rapid progression to AIDS. J Gen Virol 1997; 78(Pt 8):1913–1918.

    PubMed  Google Scholar 

  223. Venet A, Bourgault I, Aubertin AM et al. Cytotoxic T-lymphocyte response against multiple simian immunodeficiency virusA (SIV) proteins in SIV-infected macaques. J Immunol 1992; 148:2899–2908.

    CAS  PubMed  Google Scholar 

  224. Re MC, Furlini G, Vignoli M et al. Effect of antibody to HIV-1 Tat protein on viral replication in vitro and progression of HIV-1 disease in vivo. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 10:408–416.

    Article  CAS  PubMed  Google Scholar 

  225. Reiss P, Lange JM, de Ronde A et al. Speed of progression to AIDS and degree of antibody response to accessory gene products of HIV-1. J Med Virol 1990; 30:163–168.

    Article  CAS  PubMed  Google Scholar 

  226. Rezza G, Fiorelli V, Dorrucci M et al. The presence of anti-Tat antibodies is predictive of long-term nonprogression to AIDS or severe immunodeficiency: findings in a cohort of HIV-1 seroconverters. J Infect Dis 2005; 191:1321–1324.

    Article  PubMed  Google Scholar 

  227. Rodman TC, To SE, Hashish H et al. Epitopes for natural antibodies of human immunodeficiency virus (HIV)-negative (normal) and HIV-positive sera are coincident with two key functional sequences of HIV Tat protein. Proc Natl Acad Sci USA 1993; 90:7719–7723.

    Article  CAS  PubMed  Google Scholar 

  228. Zagury D, Lachgar A, Chams V et al. Interferon alpha and Tat involvement in the immunosuppression of uninfected T-cells and C−C chemokine decline in AIDS. Proc Natl Acad Sci USA 1998; 95:3851–3856.

    Article  CAS  PubMed  Google Scholar 

  229. Cafaro A, Caputo A, Fracasso C et al. Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nat Med 1999; 5:643–650.

    Article  CAS  PubMed  Google Scholar 

  230. Cafaro A, Titti F, Fracasso C et al. Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P). Vaccine 2001; 19:2862–2877.

    Article  CAS  PubMed  Google Scholar 

  231. Goldstein G, Manson K, Tribbick G et al. Minimization of chronic plasma viremia in rhesus macaques immunized with synthetic HIV-1 Tat peptides and infected with a chimeric simian/human immunodeficiency virus (SHIV33). Vaccine 2000; 18:2789–2795.

    Article  CAS  PubMed  Google Scholar 

  232. Maggiorella MT, Baroncelli S, Michelini Z et al. Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys. Vaccine 2004; 22:3258–3269.

    Article  CAS  PubMed  Google Scholar 

  233. Pauza CD, Trivedi P, Wallace M et al. Vaccination with tat toxoid attenuates disease in simian/HIV-challenged macaques. Proc Natl Acad Sci USA 2000; 97:3515–3519.

    Article  CAS  PubMed  Google Scholar 

  234. Allen TM, Mortara L, Mothe BR et al. Tat-vaccinated macaques do not control simian immunodeficiency virus SIVmac239 replication. J Virol 2002; 76:4108–4112.

    Article  CAS  PubMed  Google Scholar 

  235. Liang X, Casimiro DR, Schleif WA et al. Vectored Gag and Env but not Tat show efficacy against simian-human immunodeficiency virus 89.6P challenge in Mamu-A*01-negative rhesus monkeys. J Virol 2005; 79:12321–12331.

    Article  CAS  PubMed  Google Scholar 

  236. Silvera P, Richardson MW, Greenhouse J et al. Outcome of simian-human immunodeficiency virus strain 89.6p challenge following vaccination of rhesus macaques with human immunodeficiency virus Tat protein. J Virol 2002; 76:3800–3809.

    Article  CAS  PubMed  Google Scholar 

  237. Titti F, Cafaro A, Ferrantelli F et al. Problems and emerging approaches in HIV/AIDS vaccine development. Expert Opin Emerg Drugs 2007; 12:23–48.

    Article  CAS  PubMed  Google Scholar 

  238. Michienzi A, De Angelis FG, Bozzoni I et al. A nucleolar localizing Rev binding element inhibits HIV replication. AIDS Res Ther 2006; 3:13.

    Article  PubMed  CAS  Google Scholar 

  239. de Oliveira T, Salemi M, Gordon M et al. Mapping sites of positive selection and amino acid diversification in the HIV genome: an alternative approach to vaccine design? Genetics 2004; 167:1047–1058.

    Article  PubMed  CAS  Google Scholar 

  240. Osterhaus AD, van Baalen CA, Gruters RA et al. Vaccination with Rev and Tat against AIDS. Vaccine 1999; 17:2713–2714.

    Article  CAS  PubMed  Google Scholar 

  241. Calarota S, Bratt G, Nordlund S et al. Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients. Lancet 1998; 351:1320–1325.

    Article  CAS  PubMed  Google Scholar 

  242. Calarota SA, Leandersson AC, Bratt G et al. Immune responses in asymptomatic HIV-1-infected patients after HIV-DNA immunization followed by highly active anti-retroviral treatment. J Immunol 1999; 163:2330–2338.

    CAS  PubMed  Google Scholar 

  243. Calarota SA, Weiner DB. Approaches for the design and evaluation of HIV-1 DNA vaccines. Expert Rev Vaccines 2004; 3:S135–S149.

    Article  CAS  PubMed  Google Scholar 

  244. Kaminchik J, Bashan N, Itach A et al. Genetic characterization of human immunodeficiency virus type 1 nef gene products translated in vitro and expressed in mammalian cells. J Virol 1991; 65:583–588.

    CAS  PubMed  Google Scholar 

  245. Yu G, Felsted RL. Effect of myristoylation on p27 nef subcellular distribution and suppression of HIV-LTR transcription. Virology 1992; 187:46–55.

    Article  CAS  PubMed  Google Scholar 

  246. Piguet V, Schwartz O, Le GS et al. The downregulation of CD4 and MHC-I by primate lentiviruses: a paradigm for the modulation of cell surface receptors. Immunol Rev 1999; 168:51–63.

    Article  CAS  PubMed  Google Scholar 

  247. Arold ST, Baur AS. Dynamic Nef and Nef dynamics: how structure could explain the complex activities of this small HIV protein. Trends Biochem Sci 2001; 26:356–363.

    Article  CAS  PubMed  Google Scholar 

  248. Fackler OT, Baur AS. Live and let die: Nef functions beyond HIV replication. Immunity 2002; 16:493–497.

    Article  CAS  PubMed  Google Scholar 

  249. Qiao X, He B, Chiu A et al. Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B-cells. Nat Immunol 2006; 7:302–310.

    Article  CAS  PubMed  Google Scholar 

  250. Sol-Foulon N, Moris A, Nobile C et al. HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte clustering and viral spread. Immunity 2002; 16:145–155.

    Article  CAS  PubMed  Google Scholar 

  251. Quaranta MG, Mattioli B, Giordani L et al. The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS. FASEB J 2006; 20:2198–2208.

    Article  CAS  PubMed  Google Scholar 

  252. Xu XN, Screaton GR, Gotch FM et al. Evasion of cytotoxic T-lymphocyte (CTL) responses by nef-dependent induction of Fas ligand (CD95L) expression on simian immunodeficiency virus-infected cells. J Exp Med 1997; 186:7–16.

    Article  CAS  PubMed  Google Scholar 

  253. Geleziunas R, Xu W, Takeda K et al. HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell. Nature 2001; 410:834–838.

    Article  CAS  PubMed  Google Scholar 

  254. Schiavoni I, Trapp S, Santarcangelo AC et al. HIV-1 Nef enhances both membrane expression and virion incorporation of Env products. A model for the Nef-dependent increase of HIV-1 infectivity1. J Biol Chem 2004; 279:22996–23006.

    Article  CAS  PubMed  Google Scholar 

  255. Asakura Y, Hamajima K, Fukushima J et al. Induction of HIV-1 Nef-specific cytotoxic T-lymphocytes by Nef-expressing DNA vaccine. Am J Hematol 1996; 53:116–117.

    Article  CAS  PubMed  Google Scholar 

  256. Cosma A, Nagaraj R, Buhler S et al. Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals. Vaccine 2003; 22:21–29.

    Article  CAS  PubMed  Google Scholar 

  257. Muthumani K, Bagarazzi M, Conway D et al. Inclusion of Vpr accessory gene in a plasmid vaccine cocktail markedly reduces Nef vaccine effectiveness in vivo resulting in CD4 cell loss and increased viral loads in rhesus macaques. J Med Primatol 2002; 31:179–185.

    Article  CAS  PubMed  Google Scholar 

  258. Ensoli B, Cafaro A, Caputo A et al. Vaccines based on the native HIV Tat protein and on the combination of Tat and the structural HIV protein variant DeltaV2 Env. Microbes Infect 2005; 7:1392–1399.

    Article  CAS  PubMed  Google Scholar 

  259. Ensoli B. Rational vaccine strategies against AIDS: background and rationale. Microbes Infect 2005; 7:1445–1452.

    Article  PubMed  Google Scholar 

  260. Ensoli B. Criteria for selection of HIV vaccine candidates—general principles. Microbes Infect 2005; 7:1433–1435.

    Article  PubMed  Google Scholar 

  261. Erfle V, Goebel FD, Guzman CA et al. Vaccines based on Nef and on Nef/DeltaV2 Env. Microbes Infect 2005; 7:1400–1404.

    Article  CAS  PubMed  Google Scholar 

  262. Krohn K, Stanescu I, Blazevic V et al. A DNA HIV-1 vaccine based on a fusion gene expressing nonstructural and structural genes of consensus sequence of the A-C subtypes and the ancestor sequence of the F-H subtypes. Preclinical and clinical studies. Microbes Infect 2005; 7:1405–1413.

    CAS  PubMed  Google Scholar 

  263. Rollman E, Brave A, Boberg A et al. The rationale behind a vaccine based on multiple HIV antigens. Microbes Infect 2005; 7:1414–1423.

    CAS  PubMed  Google Scholar 

  264. Caputo A, Brocca-Cofano E, Castaldello A et al. Characterization of immune responses elicited in mice by intranasal co-immunization with HIV-1 Tat, gp140 deltaV2Env and/or SIV Gag proteins and the nontoxicogenic heat-labile Escherichia coli enterotoxin. Vaccine, epub ahead of print.

    Google Scholar 

  265. Demberg T, Florese RH, Heath MJ et al. A replication-competent adenovirus-human immunodeficiency virus (Ad-HIV) tat and Ad-HIV env priming/Tat and envelope protein boosting regimen elicits enhanced protective efficacy against simian/human immunodeficiency virus SHIV89.6P challenge in rhesus macaques. J Virol 2007; 81:3414–3427.

    Article  CAS  PubMed  Google Scholar 

  266. Sandstrom E, Wahren B, Hejdeman B et al. Improved modes of delivering a safe and highly immunogenic multigene multiclade HIV-1 DNA plasmid vaccine boosted with HIV-1 MVA (Poster 0A02-03, oral presentation, AIDS VAccine Conference, Seattle, Washington—USA; 2007).

    Google Scholar 

  267. Bakari M. The HIVIS project is a north-south collaborative study of the safety and immunogenicity of a multigene, multiclade HIV-1 plasmid DNA prime and MVA vaccine boost (EDCTP Forum, Sweden; http://www.edctp.org/fileadmin/documents/EDCTP_3rd_Forum_Report_2006.pdf).

    Google Scholar 

  268. Fischer W, Perkins S, Theiler J et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med 2007; 13:100–106.

    Article  CAS  PubMed  Google Scholar 

  269. Musey L, Ding Y, Elizaga M et al. HIV-1 vaccination administered intramuscularly can induce both systemic and mucosal T-cell immunity in HIV-1-uninfected individuals. J Immunol 2003; 171:1094–1101.

    CAS  PubMed  Google Scholar 

  270. Haase AT. Perils at mucosal front lines for HIV and SIV and their hosts. Nat Rev Immunol 2005; 5:783–792.

    CAS  PubMed  Google Scholar 

  271. Mattapallil JJ, Douek DC, Hill B et al. Massive infection and loss of memory CD4+ T-cells in multiple tissues during acute SIV infection. Nature 2005; 434:1093–1097.

    Article  CAS  PubMed  Google Scholar 

  272. Veazey RS, DeMaria M, Chalifoux LV et al. Gastrointestinal tract as a major site of CD4+ T-cell depletion and viral replication in SIV infection. Science 1998; 280:427–431.

    Article  CAS  PubMed  Google Scholar 

  273. Veazey RS, Marx PA, Lackner AA. Vaginal CD4+ T-cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection. J Infect Dis 2003; 187:769–776.

    Article  CAS  PubMed  Google Scholar 

  274. Bomsel M, Heyman M, Hocini H et al. Intracellular neutralization of HIV transcytosis across tight epithelial barriers by anti-HIV envelope protein dIgA or IgM. Immunity 1998; 9:277–287.

    Article  CAS  PubMed  Google Scholar 

  275. Lo CS, Trabattoni D, Vichi F et al. Mucosal and systemic HIV-1-specific immunity in HIV-1-exposed but uninfected heterosexual men. AIDS 2003; 17:531–539.

    Article  Google Scholar 

  276. Murphey-Corb M, Wilson LA, Trichel AM et al. Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa. J Immunol 1999; 162:540–549.

    CAS  PubMed  Google Scholar 

  277. Belyakov IM, Kuznetsov VA, Kelsall B et al. Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa. Blood 2006; 107:3258–3264.

    Article  CAS  PubMed  Google Scholar 

  278. Belyakov IM, Isakov D, Zhu Q et al. A novel functional CTL avidity/activity compartmentalization to the site of mucosal immunization contributes to protection of macaques against simian/human immunodeficiency viral depletion of mucosal CD4+ T-cells. J Immunol 2007; 178:7211–7221.

    CAS  PubMed  Google Scholar 

  279. Belyakov IM, Hel Z, Kelsall B et al. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat Med 2001; 7:1320–1326.

    Article  CAS  PubMed  Google Scholar 

  280. Vajdy M. Induction of optimal immune responses against human immunodeficiency virus at mucosal portals of entry. Curr Drug Targets Immune Endocr Metabol Disord 2003; 3:222–233.

    Article  CAS  PubMed  Google Scholar 

  281. Kubota M, Miller CJ, Imaoka K et al. Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates. J Immunol 1997; 158:5321–5329.

    CAS  PubMed  Google Scholar 

  282. Russell MW, Mestecky J. Humoral immune responses to microbial infections in the genital tract. Microbes Infect 2002; 4:667–677.

    Article  CAS  PubMed  Google Scholar 

  283. Asanuma H, Aizawa C, Kurata T et al. IgA antibody-forming cell responses in the nasal-associated lymphoid tissue of mice vaccinated by intranasal, intravenous and/or subcutaneous administration. Vaccine 1998; 16:1257–1262.

    Article  CAS  PubMed  Google Scholar 

  284. Lowell GH, Kaminski RW, VanCott TC et al. Proteosomes, emulsomes and cholera toxin B improve nasal immunogenicity of human immunodeficiency virus gp160 in mice: induction of serum, intestinal, vaginal and lung IgA and IgG. J Infect Dis 1997; 175:292–301.

    CAS  PubMed  Google Scholar 

  285. Bergquist C, Johansson EL, Lagergard T et al. Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina. Infect Immun 1997; 65:2676–2684.

    CAS  PubMed  Google Scholar 

  286. Imaoka K, Miller CJ, Kubota M et al. Nasal immunization of nonhuman primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for virus-specific immune responses in reproductive tissues. J Immunol 1998; 161:5952–5958.

    CAS  PubMed  Google Scholar 

  287. Medaglini D, Ciabattini A, Cuppone AM et al. In vivo activation of naive CD4+ T-cells in nasal mucosa-associated lymphoid tissue following intranasal immunization with recombinant Streptococcus gordonii. Infect Immun 2006; 74:2760–2766.

    Article  CAS  PubMed  Google Scholar 

  288. Pialoux G, Hocini H, Perusat S et al. Phase I study of a candidate vaccine based on recombinant HIV-1 gp160 (MN/LAI) administered by the mucosal route to HIV-seronegative volunteers: The ANRS VAC14 study. Vaccine 2007; Epub ahead of print.

    Google Scholar 

  289. Vajdy M, Singh M. Intranasal delivery of vaccines against HIV. Expert Opin Drug Deliv 2006; 3:247–259.

    Article  CAS  PubMed  Google Scholar 

  290. Tenner-Racz K, Stahl HC, Uberla K et al. Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus. Proc Natl Acad Sci USA 2004; 101:3017–3022.

    Article  CAS  PubMed  Google Scholar 

  291. Bruhl P, Kerschbaum A, Eibl MM et al. An experimental prime-boost regimen leading to HIV type 1-specific mucosal and systemic immunity in BALB/c mice. AIDS Res Hum Retroviruses 1998; 14:401–407.

    Article  CAS  PubMed  Google Scholar 

  292. Eo SK, Gierynska M, Kamar AA et al. Prime-boost immunization with DNA vaccine: mucosal route of administration changes the rules. J Immunol 2001; 166:5473–5479.

    CAS  PubMed  Google Scholar 

  293. Mantis NJ, Kozlowski PA, Mielcarz DW et al. Immunization of mice with recombinant gp41 in a systemic prime/mucosal boost protocol induces HIV-1-specific serum IgG and secretory IgA antibodies. Vaccine 2001; 19:3990–4001.

    Article  CAS  PubMed  Google Scholar 

  294. McCluskie MJ, Weeratna RD, Payette PJ et al. Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA. FEMS Immunol Med Microbiol 2002; 32:179–185.

    Article  CAS  PubMed  Google Scholar 

  295. Hladik F, Sakchalathorn P, Ballweber L et al. Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 2007; 26:257–270.

    Article  CAS  PubMed  Google Scholar 

  296. Lanzavecchia A, Sallusto F. The instructive role of dendritic cells on T-cell responses: lineages, plasticity and kinetics. Curr Opin Immunol 2001; 13:291–298.

    Article  CAS  PubMed  Google Scholar 

  297. Mellman I, Steinman RM. Dendritic cells: specialized and regulated antigen processing machines. Cell 2001; 106:255–258.

    Article  CAS  PubMed  Google Scholar 

  298. Zhu Q, Thomson CW, Rosenthal KL et al. Immunization with adenovirus at the large intestinal mucosa as an effective vaccination strategy against sexually transmitted viral infection. Mucosal Immunol 2008; 1:78–88.

    Article  CAS  PubMed  Google Scholar 

  299. Andrieu JM, Lu W. A dendritic cell-based vaccine for treating HIV infection: background and preliminary results. J Intern Med 2007; 261:123–131.

    Article  CAS  PubMed  Google Scholar 

  300. Bozzacco L, Trumpfheller C, Siegal FP et al. DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T-cells in a spectrum of human MHC I haplotypes. Proc Natl Acad Sci USA 2007; 104:1289–1294.

    Article  CAS  PubMed  Google Scholar 

  301. Brown K, Gao W, Alber S et al. Adenovirus-transduced dendritic cells injected into skin or lymph node prime potent simian immunodeficiency virus-specific T-cell immunity in monkeys. J Immunol 2003; 171:6875–6882.

    CAS  PubMed  Google Scholar 

  302. Carbonneil C, Aouba A, Burgard M et al. Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-alpha are potent inducers of HIV-specific CD8 T-cells. AIDS 2003; 17:1731–1740.

    Article  CAS  PubMed  Google Scholar 

  303. Gruber A, Chalmers AS, Rasmussen RA et al. Dendritic cell-based vaccine strategy against human immunodeficiency virus clade C: skewing the immune response toward a helper T-cell type 2 profile. Viral Immunol 2007; 20:160–169.

    Article  CAS  PubMed  Google Scholar 

  304. Lisziewicz J, Trocio J, Whitman L et al. DermaVir: a novel topical vaccine for HIV/AIDS. J Invest Dermatol 2005; 124:160–169.

    Article  CAS  PubMed  Google Scholar 

  305. Melhem NM, Liu XD, Boczkowski D et al. Robust CD4+ and CD8+ T-cell responses to SIV using mRNA-transfected DC expressing autologous viral Ag. Eur J Immunol 2007; 37:2164–2173.

    Article  CAS  PubMed  Google Scholar 

  306. Nehete PN, Nehete BP, Manuri P et al. Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model. Vaccine 2005; 23:2154–2159.

    Article  CAS  PubMed  Google Scholar 

  307. Lu W, Wu X, Lu Y et al. Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med 2003; 9:27–32.

    Article  CAS  PubMed  Google Scholar 

  308. Lu W, Arraes LC, Ferreira WT et al. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 2004; 10:1359–1365.

    Article  CAS  PubMed  Google Scholar 

  309. Veljkovic V, Prljic J, Veljkovic T. Safety and ethical consideration of AIDS vaccine. Int Rev Immunol 2004; 23:465–486.

    Article  CAS  PubMed  Google Scholar 

  310. Burton DR, Desrosiers RC, Doms RW et al. HIV vaccine design and the neutralizing antibody problem. Nat Immunol 2004; 5:233–236.

    Article  CAS  PubMed  Google Scholar 

  311. Hokey DA, Weiner DB. DNA vaccines for HIV: challenges and opportunities. Springer Semin Immunopathol 2006; 28:267–279.

    Article  CAS  PubMed  Google Scholar 

  312. Barouch DH, Craiu A, Kuroda MJ et al. Augmentation of immune responses to HIV-1 and simian immunodeficiency virus DNA vaccines by IL-2/Ig plasmid administration in rhesus monkeys. Proc Natl Acad Sci USA 2000; 97:4192–4197.

    Article  CAS  PubMed  Google Scholar 

  313. Letvin NL, Montefiori DC, Yasutomi Y et al. Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination. Proc Natl Acad Sci USA 1997; 94:9378–9383.

    Article  CAS  PubMed  Google Scholar 

  314. MacGregor RR, Ginsberg R, Ugen KE et al. T-cell responses induced in normal volunteers immunized with a DNA-based vaccine containing HIV-1 env and rev. AIDS 2002; 16:2137–2143.

    Article  CAS  PubMed  Google Scholar 

  315. Calarota SA, Weiner DB. Enhancement of human immunodeficiency virus type 1-DNA vaccine potency through incorporation of T-helper 1 molecular adjuvants. Immunol Rev 2004; 199:84–99.

    Article  CAS  PubMed  Google Scholar 

  316. Lori F, Weiner DB, Calarota SA et al. Cytokine-adjuvanted HIV-DNA vaccination strategies. Springer Semin Immunopathol 2006; 28:231–238.

    Article  CAS  PubMed  Google Scholar 

  317. Chen WC, Huang L. Nonviral vector as vaccine carrier. Adv Genet 2005; 54:315–337.

    Article  CAS  PubMed  Google Scholar 

  318. Greenland JR, Liu H, Berry D et al. Beta-amino ester polymers facilitate in vivo DNA transfection and adjuvant plasmid DNA immunization. Mol Ther 2005; 12:164–170.

    Article  CAS  PubMed  Google Scholar 

  319. Sumida SM, McKay PF, Truitt DM et al. Recruitment and expansion of dendritic cells in vivo potentiate the immunogenicity of plasmid DNA vaccines. J Clin Invest 2004; 114:1334–1342.

    CAS  PubMed  Google Scholar 

  320. Eller MA, Eller LA, Opollo MS et al. Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans. Vaccine 2007; 25:7737–7742.

    Article  CAS  PubMed  Google Scholar 

  321. Graham BS, Koup RA, Roederer M et al. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis 2006; 194:1650–1660.

    Article  CAS  PubMed  Google Scholar 

  322. Launay O, Durier C, Desaint C et al. Cellular immune responses induced with dose-sparing intradermal administration of HIV vaccine to HIV-uninfected volunteers in the ANRS VAC16 trial. PLoS ONE 2007; 2:e725.

    Article  PubMed  Google Scholar 

  323. Dietrich G, Spreng S, Favre D et al. Live attenuated bacteria as vectors to deliver plasmid DNA vaccines. Curr Opin Mol Ther 2003; 5:10–19.

    PubMed  Google Scholar 

  324. Daudel D, Weidinger G, Spreng S. Use of attenuated bacteria as delivery vectors for DNA vaccines. Expert Rev Vaccines 2007; 6:97–110.

    Article  CAS  PubMed  Google Scholar 

  325. Schodel F, Curtiss R, III. Salmonellae as oral vaccine carriers. Dev Biol Stand 1995; 84:245–253.

    CAS  PubMed  Google Scholar 

  326. Russmann H, Shams H, Poblete F et al. Delivery of epitopes by the Salmonella type III secretion system for vaccine development. Science 1998; 281:565–568.

    Article  CAS  PubMed  Google Scholar 

  327. Evans DT, Chen LM, Gillis J et al. Mucosal priming of simian immunodeficiency virus-specific cytotoxic T-lymphocyte responses in rhesus macaques by the Salmonella type III secretion antigen delivery system. J Virol 2003; 77:2400–2409.

    Article  CAS  PubMed  Google Scholar 

  328. Kotton CN, Lankowski AJ, Scott N et al. Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimutium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system. Vaccine 2006; 24:6216–6224.

    Article  CAS  PubMed  Google Scholar 

  329. Tsunetsugu-Yokota Y, Ishige M, Murakami M. Oral attenuated Salmonella enterica serovar Typhimurium vaccine expressing codon-optimized HIV type 1 Gag enhanced intestinal immunity in mice. AIDS Res Hum Retroviruses 2007; 23:278–286.

    Article  CAS  PubMed  Google Scholar 

  330. Joseph J, Saubi N, Pezzat E et al. Progress towards an HIV vaccine based on recombinant bacillus Calmette-Guerin: failures and challenges. Expert Rev Vaccines 2006; 5:827–838.

    Article  CAS  PubMed  Google Scholar 

  331. Honda M, Matsuo K, Nakasone T et al. Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette-Guerin vector candidate vaccine for human immunodeficiency virus type 1 in small animals. Proc Natl Acad Sci USA 1995; 92:10693–10697.

    Article  CAS  PubMed  Google Scholar 

  332. Yasutomi Y, Koenig S, Haun SS et al. Immunization with recombinant BCG-SIV elicits SIV-specific cytotoxic T-lymphocytes in rhesus monkeys. J Immunol 1993; 150:3101–3107.

    CAS  PubMed  Google Scholar 

  333. Someya K, Cecilia D, Ami Y et al. Vaccination of rhesus macaques with recombinant Mycobacterium bovis bacillus Calmette-Guerin Env V3 elicits neutralizing antibody-mediated protection against simian-human immunodeficiency virus with a homologous but not a heterologous V3 motif. J Virol 2005; 79:1452–1462.

    Article  CAS  PubMed  Google Scholar 

  334. Falk LA, Goldenthal KL, Esparza J et al. Recombinant bacillus Calmette-Guerin as a potential vector for preventive HIV type 1 vaccines. AIDS Res Hum Retroviruses 2000; 16:91–98.

    Article  CAS  PubMed  Google Scholar 

  335. Enserink M. Public health. In the HIV era, an old TB vaccine causes new problems. Science 2007; 318:1059.

    Article  CAS  PubMed  Google Scholar 

  336. Paterson Y, Johnson RS. Progress towards the use of Listeria monocytogenes as a live bacterial vaccine vector for the delivery of HIV antigens. Expert Rev Vaccines 2004; 3:S119–S134.

    Article  CAS  PubMed  Google Scholar 

  337. Guzman CA, Saverino D, Medina E et al. Attenuated Listeria monocytogenes carrier strains can deliver an HIV-1 gp120 T-helper epitope to MHC class II-restricted human CD4+ T-cells. Eur J Immunol 1998; 28:1807–1814.

    Article  CAS  PubMed  Google Scholar 

  338. Paterson Y, Maciag PC. Listeria-based vaccines for cancer treatment. Curr Opin Mol Ther 2005; 7:454–460.

    CAS  PubMed  Google Scholar 

  339. Yewdell JW. The seven dirty little secrets of major histocompatibility complex class I antigen processing. Immunol Rev 2005; 207:8–18.

    Article  CAS  PubMed  Google Scholar 

  340. Manohar M, Baumann DO, Bos NA et al. Gut colonization of mice with actA-negative mutant of Listeria monocytogenes can stimulate a humoral mucosal immune response. Infect Immun 2001; 69:3542–3549.

    Article  CAS  PubMed  Google Scholar 

  341. Frankel FR, Hegde S, Lieberman J et al. Induction of cell-mediated immune responses to human immunodeficiency virus type 1 Gag protein by using Listeria monocytogenes as a live vaccine vector. J Immunol 1995; 155:4775–4782.

    CAS  PubMed  Google Scholar 

  342. Boyer JD, Robinson TM, Maciag PC et al. DNA prime Listeria boost induces a cellular immune response to SIV antigens in the rhesus macaque model that is capable of limited suppression of SIV239 viral replication. Virology 2005; 333:88–101.

    Article  CAS  PubMed  Google Scholar 

  343. Brockstedt DG, Giedlin MA, Leong ML et al. Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci USA 2004; 101:13832–13837.

    Article  CAS  PubMed  Google Scholar 

  344. Brockstedt DG, Bahjat KS, Giedlin MA et al. Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity. Nat Med 2005; 11:853–860.

    Article  CAS  PubMed  Google Scholar 

  345. Starks H, Bruhn KW, Shen H et al. Listeria monocytogenes as a vaccine vector: virulence attenuation or existing anti-vector immunity does not diminish therapeutic efficacy. J Immunol 2004; 173:420–427.

    CAS  PubMed  Google Scholar 

  346. Yoshimura K, Jain A, Allen HE et al. Selective targeting of anti-tumor immune responses with engineered live-attenuated Listeria monocytogenes. Cancer Res 2006; 66:1096–1104.

    Article  CAS  PubMed  Google Scholar 

  347. Jiang S, Rasmussen RA, Nolan KM et al. Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys. Vaccine 2007; 25:7470–7479.

    Article  CAS  PubMed  Google Scholar 

  348. Neeson P, Boyer J, Kumar S et al. A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T-cell mucosal response characterized by high levels of alpha4beta7 integrin and an effector memory phenotype. Virology 2006; 354:299–315.

    Article  CAS  PubMed  Google Scholar 

  349. Learmont J, Tindall B, Evans L et al. Long-term symptomless HIV-1 infection in recipients of blood products from a single donor. Lancet 1992; 340:863–867.

    Article  CAS  PubMed  Google Scholar 

  350. Learmont J, Cook L, Dunckley H et al. Update on long-term symptomless HIV type 1 infection in recipients of blood products from a single donor. AIDS Res Hum Retroviruses 1995; 11:1.

    Article  CAS  PubMed  Google Scholar 

  351. Brave A, Gudmundsdotter L, Gasteiger G et al. Immunization of mice with the nef gene from Human Immunodeficiency Virus type 1: Study of immunological memory and long-term toxicology. Infect Agent Cancer 2007; 2:14.

    Article  PubMed  CAS  Google Scholar 

  352. Singh M, Jeang KT, Smith SM. HIV vaccine development. Front Biosci 2005; 10:2064–2081.

    Article  CAS  PubMed  Google Scholar 

  353. Gherardi MM, Esteban M. Recombinant poxviruses as mucosal vaccine vectors. J Gen Virol 2005; 86:2925–2936.

    Article  CAS  PubMed  Google Scholar 

  354. de Bruyn G, Rossini AJ, Chiu YL et al. Safety profile of recombinant canarypox HIV vaccines. Vaccine 2004; 22:704–713.

    Article  PubMed  CAS  Google Scholar 

  355. Dorrell L, Williams P, Suttill A et al. Safety and tolerability of recombinant modified vaccinia virus Ankara expressing an HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected persons receiving combination anti-retroviral therapy. Vaccine 2007; 25:3277–3283.

    Article  CAS  PubMed  Google Scholar 

  356. Gomez CE, Najera JL, Jimenez EP et al. Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1(IIIB) Gag-Pol-Nef proteins of clade B. Vaccine 2007; 25:2863–2885.

    Article  CAS  PubMed  Google Scholar 

  357. Zhang ZQ, Casimiro DR, Schleif WA et al. Early depletion of proliferating B-cells of germinal center in rapidly progressive simian immunodeficiency virus infection. Virology 2007; 361:455–464.

    Article  CAS  PubMed  Google Scholar 

  358. Amara RR, Villinger F, Altman JD et al. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 2001; 292:69–74.

    Article  CAS  PubMed  Google Scholar 

  359. Hanke T, Samuel RV, Blanchard TJ et al. Effective induction of simian immunodeficiency virus-specific cytotoxic T-lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen. J Virol 1999; 73:7524–7532.

    CAS  PubMed  Google Scholar 

  360. Hel Z, Tsai WP, Thornton A et al. Potentiation of simian immunodeficiency virus (SIV)-specific CD4(+) and CD8(+) T-cell responses by a DNA-SIV and NYVAC-SIV prime/boost regimen. J Immunol 2001; 167:7180–7191.

    CAS  PubMed  Google Scholar 

  361. Hel Z, Nacsa J, Tryniszewska E et al. Containment of simian immunodeficiency virus infection in vaccinated macaques: correlation with the magnitude of virus-specific pre and postchallenge CD4+ and CD8+ T-cell responses. J Immunol 2002; 169:4778–4787.

    PubMed  Google Scholar 

  362. Ondondo BO, Yang H, Dong T et al. Immunisation with recombinant modified vaccinia virus Ankara expressing HIV-1 gag in HIV-1-infected subjects stimulates broad functional CD4+ T-cell responses. Eur J Immunol 2006; 36:2585–2594.

    Article  CAS  PubMed  Google Scholar 

  363. Peters BS, Jaoko W, Vardas E et al. Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: effects of dosage and route on safety and immunogenicity. Vaccine 2007; 25:2120–2127.

    Article  CAS  PubMed  Google Scholar 

  364. Harrer E, Bauerle M, Ferstl B et al. Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption. Antivir Ther 2005; 10:285–300.

    CAS  PubMed  Google Scholar 

  365. Franchini G, Gurunathan S, Baglyos L et al. Poxvirus-based vaccine candidates for HIV: two decades of experience with special emphasis on canarypox vectors. Expert Rev Vaccines 2004; 3:S75–S88.

    Article  CAS  PubMed  Google Scholar 

  366. Beukema EL, Brown MP, Hayball JD. The potential role of fowlpox virus in rational vaccine design. Expert Rev Vaccines 2006; 5:565–577.

    Article  PubMed  Google Scholar 

  367. Hel Z, Nacsa J, Tsai WP et al. Equivalent immunogenicity of the highly attenuated poxvirus-based ALVAC-SIV and NYVAC-SIV vaccine candidates in SIVmac251-infected macaques. Virology 2002; 304:125–134.

    Article  CAS  PubMed  Google Scholar 

  368. Goepfert PA, Horton H, McElrath MJ et al. High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects. J Infect Dis 2005; 192:1249–1259.

    Article  CAS  PubMed  Google Scholar 

  369. Thongcharoen P, Suriyanon V, Paris RM et al. A phase 1/2 comparative vaccine trial of the safety and immunogenicity of a CRF01_AE (subtype E) candidate vaccine: ALVAC-HIV (vCP1521) prime with oligomeric gp160 (92TH023/LAI-DID) or bivalent gp120 (CM235/SF2) boost. J Acquir Immune Defic Syndr 2007; 46:48–55.

    Article  PubMed  Google Scholar 

  370. Russell ND, Graham BS, Keefer MC et al. Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial. J Acquir Immune Defic Syndr 2007; 44:203–212.

    Article  CAS  PubMed  Google Scholar 

  371. Kent SJ, Zhao A, Dale CJ et al. A recombinant avipoxvirus HIV-1 vaccine expressing interferon-gamma is safe and immunogenic in macaques. Vaccine 2000; 18:2250–2256.

    Article  CAS  PubMed  Google Scholar 

  372. Emery S, Workman C, Puls RL et al. Randomized, placebo-controlled, phase I/IIa evaluation of the safety and immunogenicity of fowlpox virus expressing HIV gag-pol and interferon-gamma in HIV-1 infected subjects. Hum Vaccin 2005; 1:232–238.

    CAS  PubMed  Google Scholar 

  373. Levy JA, Autran B, Coutinho R et al. Registration of clinical trials. AIDS 2005; 19:105.

    Article  PubMed  Google Scholar 

  374. Kelleher AD, Puls RL, Bebbington M et al. A randomized, placebo-controlled phase I trial of DNA prime, recombinant fowlpox virus boost prophylactic vaccine for HIV-1. AIDS 2006; 20:294–297.

    Article  CAS  PubMed  Google Scholar 

  375. Kent SJ, Dale CJ, Ranasinghe C et al. Mucosally-administered human-simian immunodeficiency virus DNA and fowlpoxvirus-based recombinant vaccines reduce acute phase viral replication in macaques following vaginal challenge with CCR5-tropic SHIVSF162P3. Vaccine 2005; 23:5009–5021.

    Article  CAS  PubMed  Google Scholar 

  376. D De Rose R, Sullivan MT, Dale CJ et al. Dose-response relationship of DNA and recombinant fowlpox virus prime-boost HIV vaccines: implications for future trials. Hum Vaccin 2006; 2:134–136.

    PubMed  Google Scholar 

  377. Natuk RJ, Davis AR, Chanda PK et al. Adenovirus vectored vaccines. Dev Biol Stand 1994; 82:71–77.

    CAS  PubMed  Google Scholar 

  378. Cheng C, Gall JG, Kong WP et al. Mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells. PLoS Pathog 2007; 3:e25.

    Article  PubMed  CAS  Google Scholar 

  379. Tan PH, Beutelspacher SC, Xue SA et al. Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy. Blood 2005; 105:3824–3832.

    Article  CAS  PubMed  Google Scholar 

  380. Gomez-Roman VR, Robert-Guroff M. Adenoviruses as vectors for HIV vaccines. AIDS Rev 2003; 5:178–185.

    PubMed  Google Scholar 

  381. Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type. Hum Gene Ther 2005; 16:149–156.

    Article  CAS  PubMed  Google Scholar 

  382. Peng B, Wang LR, Gomez-Roman VR et al. Replicating rather than nonreplicating adenovirus-human immunodeficiency virus recombinant vaccines are better at eliciting potent cellular immunity and priming high-titer antibodies. J Virol 2005; 79:10200–10209.

    Article  CAS  PubMed  Google Scholar 

  383. Sumida SM, Truitt DM, Lemckert AA et al. Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein. J Immunol 2005; 174:7179–7185.

    CAS  PubMed  Google Scholar 

  384. Barouch DH, Pau MG, Custers JH et al. Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity. J Immunol 2004; 172:6290–6297.

    CAS  PubMed  Google Scholar 

  385. Capone S, Meola A, Ercole BB et al. A novel adenovirus type 6 (Ad6)-based hepatitis C virus vector that overcomes preexisting anti-ad5 immunity and induces potent and broad cellular immune responses in rhesus macaques. J Virol 2006; 80:1688–1699.

    Article  CAS  PubMed  Google Scholar 

  386. Lemckert AA, Sumida SM, Holterman L et al. Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-ad5 immunity. J Virol 2005; 79:9694–9701.

    Article  CAS  PubMed  Google Scholar 

  387. Nanda A, Lynch DM, Goudsmit J et al. Immunogenicity of recombinant fiber-chimeric adenovirus serotype 35 vector-based vaccines in mice and rhesus monkeys. J Virol 2005; 79:14161–14168.

    Article  CAS  PubMed  Google Scholar 

  388. Roberts DM, Nanda A, Havenga MJ et al. Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity. Nature 2006; 441:239–243.

    Article  CAS  PubMed  Google Scholar 

  389. Xin KQ, Jounai N, Someya K et al. Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces protective immunity against HIV. Gene Ther 2005; 12:1769–1777.

    Article  CAS  PubMed  Google Scholar 

  390. von Bubnoff A. One-two combination. Heterologous prime-boost is currently the regimen of choice for many AIDS vaccine approaches, even though exactly how it works is still far from clear. IAVI Report, 2007; Vol 11[3]:11–14.

    Google Scholar 

  391. Thorner AR, Lemckert AA, Goudsmit J et al. Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity. J Virol 2006; 80:12009–12016.

    Article  CAS  PubMed  Google Scholar 

  392. Seaman MS, Xu L, Beaudry K et al. Multiclade human immunodeficiency virus type 1 envelope immunogens elicit broad cellular and, humoral immunity in rhesus monkeys. J Virol 2005; 79:2956–2963.

    Article  CAS  PubMed  Google Scholar 

  393. Malkevitch NV, Robert-Guroff M. A call for replicating vector prime-protein boost strategies in HIV vaccine design. Expert Rev Vaccines 2004; 3:S105–S117.

    Article  PubMed  Google Scholar 

  394. Buge SL, Richardson E, Alipanah S et al. An adenovirus-simian immunodeficiency virus env vaccine elicits humoral, cellular and mucosal immune responses in rhesus macaques and decreases viral burden following vaginal challenge. J Virol 1997; 71:8531–8541.

    CAS  PubMed  Google Scholar 

  395. Buge SL, Murty L, Arora K et al. Factors associated with slow disease progression in macaques immunized with an adenovirus-simian immunodeficiency virus (SIV) envelope priming-gp120 boosting regimen and challenged vaginally with SIVmac251. J Virol 1999; 73:7430–7440.

    CAS  PubMed  Google Scholar 

  396. Lubeck MD, Natuk R, Myagkikh M et al. Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization. Nat Med 1997; 3:651–658.

    Article  CAS  PubMed  Google Scholar 

  397. Malkevitch N, Patterson LJ, Aldrich K et al. A replication competent adenovirus 5 host range mutant-simian immunodeficiency virus (SIV) recombinant priming/subunit protein boosting vaccine regimen induces broad, persistent SIV-specific cellular immunity to dominant and subdominant epitopes in Mamu-A*01 rhesus macaques. J Immunol 2003; 170:4281–4289.

    CAS  PubMed  Google Scholar 

  398. Patterson LJ, Malkevitch N, Pinczewski J et al. Potent, persistent induction and modulation of cellular immune responses in rhesus macaques primed with Ad5hr-simian immunodeficiency virus (SIV) env/rev, gag and/or nef vaccines and boosted with SIV gp120. J Virol 2003; 77:8607–8620.

    Article  CAS  PubMed  Google Scholar 

  399. Pinczewski J, Zhao J, Malkevitch N et al. Enhanced immunity and protective efficacy against SIVmac251 intrarectal challenge following ad-SIV priming by multiple mucosal routes and gp120 boosting in MPL-SE. Viral Immunol 2005; 18:236–243.

    Article  CAS  PubMed  Google Scholar 

  400. Zhao J, Voltan R, Peng B et al. Enhanced cellular immunity to SIV Gag following co-administration of adenoviruses encoding wild-type or mutant HIV Tat and SIV Gag. Virology 2005; 342:1–12.

    Article  CAS  PubMed  Google Scholar 

  401. Zolla-Pazner S, Lubeck M, Xu S et al. Induction of neutralizing antibodies to T-cell line-adapted and primary human immunodeficiency virus type 1 isolates with a prime-boost vaccine regimen in chimpanzees. J Virol 1998; 72:1052–1059.

    CAS  PubMed  Google Scholar 

  402. Johnson PR, Schnepp BC, Connell MJ et al. Novel adeno-associated virus vector vaccine restricts replication of simian immunodeficiency virus in macaques. J Virol 2005; 79:955–965.

    Article  CAS  PubMed  Google Scholar 

  403. Lai CM, Lai YK, Rakoczy PE. Adenovirus and adeno-associated virus vectors. DNA Cell Biol 2002; 21:895–913.

    Article  CAS  PubMed  Google Scholar 

  404. van Lunzen J, Mehendale S, Clumeck N et al. A phase I to evaluate the safety and immunogenicity of a recombinant adeno-associated virus vaccine (Abstract #474 presented at the 14th CROI, Los Angeles 2007 http://www.retroconference.org/2007).

    Google Scholar 

  405. Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation and cancer. J Clin Invest 2007; 117:1175–1183.

    Article  CAS  PubMed  Google Scholar 

  406. Souza AP, Haut L, Reyes-Sandoval A et al. Recombinant viruses as vaccines against viral diseases. Braz J Med Biol Res 2005; 38:509–522.

    Article  CAS  PubMed  Google Scholar 

  407. Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998; 392:86–89.

    Article  CAS  PubMed  Google Scholar 

  408. MacDonald GH, Johnston RE. Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis. J Virol 2000; 74:914–922.

    Article  CAS  PubMed  Google Scholar 

  409. Davis NL, West A, Reap E et al. Alphavirus replicon particles as candidate HIV vaccines. IUBMB Life 2002; 53:209–211.

    Article  CAS  PubMed  Google Scholar 

  410. McKenna PM, McGettigan JP, Pomerantz RJ et al. Recombinant rhabdoviruses as potential vaccines for HIV-1 and other diseases. Curr HIV Res 2003; 1:229–237.

    Article  CAS  PubMed  Google Scholar 

  411. Publicover J, Ramsburg E, Rose JK. A single-cycle vaccine vector based on vesicular stomatitis virus can induce immune responses comparable to those generated by a replication-competent vector. J Virol 2005; 79:13231–13238.

    Article  CAS  PubMed  Google Scholar 

  412. Egan MA, Chong SY, Rose NF et al. Immunogenicity of attenuated vesicular stomatitis virus vectors expressing HIV type 1 Env and SIV Gag proteins: comparison of intranasal and intramuscular vaccination routes. AIDS Res Hum Retroviruses 2004; 20:989–1004.

    Article  CAS  PubMed  Google Scholar 

  413. Rose NF, Marx PA, Luckay A et al. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell 2001; 106:539–549.

    Article  CAS  PubMed  Google Scholar 

  414. Clarke DK, Cooper D, Egan MA et al. Recombinant vesicular stomatitis virus as an, HIV-1 vaccine vector. Springer Semin Immunopathol 2006; 28:239–253.

    Article  CAS  PubMed  Google Scholar 

  415. Cooper D, Wright KJ, Calderon PC et al. Attenuation of recombinant vesicular stomatitis virus-human immunodeficiency virus type 1 vaccine vectors by gene translocations and g gene truncation reduces neurovirulence and enhances immunogenicity in mice. J Virol 2008; 82:207–219.

    Article  CAS  PubMed  Google Scholar 

  416. Crotty S, Andino R. Poliovirus vaccine strains as mucosal vaccine vectors and their potential use to develop an, AIDS vaccine. Adv Drug Deliv Rev 2004; 56:835–852.

    Article  CAS  PubMed  Google Scholar 

  417. Crotty S, Miller CJ, Lohman BL et al. Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors. J Virol 2001; 75:7435–7452.

    Article  CAS  PubMed  Google Scholar 

  418. Mueller S, Wimmer E. Expression of foreign proteins by poliovirus polyprotein fusion: analysis of genetic stability reveals rapid deletions and formation of cardioviruslike open reading frames. J Virol 1998; 72:20–31.

    CAS  PubMed  Google Scholar 

  419. Murphy CG, Lucas WT, Means RE et al. Vaccine protection against simian immunodeficiency virus by recombinant strains of herpes simplex virus. J Virol 2000; 74:7745–7754.

    Article  CAS  PubMed  Google Scholar 

  420. Kaur A, Sanford HB, Garry D et al. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus. Virology 2007; 357:199–214.

    Article  CAS  PubMed  Google Scholar 

  421. O’Hagan DT, Singh M. Microparticles as vaccine adjuvants and delivery systems. Expert Rev Vaccines 2003; 2:269–283.

    Article  PubMed  Google Scholar 

  422. O’Hagan DT, Singh M, Ulmer JB. Microparticles for the delivery of DNA vaccines. Immunol Rev 2004; 199:191–200.

    Article  PubMed  Google Scholar 

  423. Johansen P, Men Y, merkle HP et al. Revisiting PLA/PLGA microspheres: an analysis of their potential in parenteral vaccination. Eur J Pharm Biopharm 2000; 50:129–146.

    Article  CAS  PubMed  Google Scholar 

  424. Bowersock TL, HogenEsch H, Suckow M et al. Oral vaccination of animals with antigens encapsulated in alginate microspheres. Vaccine 1999; 17:1804–1811.

    Article  CAS  PubMed  Google Scholar 

  425. O’Hagan DT, Singh M, Ulmer JB. Microparticle-based technologies for vaccines. Methods 2006; 40:10–19.

    Article  PubMed  CAS  Google Scholar 

  426. Johansen P, Martinez Gomez JM, Gander B. Development of synthetic biodegradable microparticulate vaccines: a roller coaster story. Expert Rev Vaccines 2007; 6:471–474.

    Article  CAS  PubMed  Google Scholar 

  427. Otten GR, Schaefer M, Doe B et al. Enhanced potency of plasmid DNA microparticle human immunodeficiency virus vaccines in rhesus macaques by using a priming-boosting regimen with recombinant proteins. J Virol 2005; 79:8189–8200.

    Article  CAS  PubMed  Google Scholar 

  428. Caputo A, Brocca-Cofano E, Castaldello A et al. Novel biocompatible anionic polymeric microspheres for the delivery of the HIV-1 Tat protein for vaccine application. Vaccine 2004; 22:2910–2924.

    Article  CAS  PubMed  Google Scholar 

  429. Castaldello A, Brocca-Cofano E, Voltan R et al. DNA prime and protein boost immunization with innovative polymeric cationic core-shell nanoparticles elicits broad immune responses and strongly enhance cellular responses of HIV-1 tat DNA vaccination. Vaccine 2006; 24:5655–5669.

    Article  CAS  PubMed  Google Scholar 

  430. Voltan R, Castaldello A, Brocca-Cofano E et al. Preparation and characterization of innovative protein-coated poly(methylmethacrylate) core-shell nanoparticles for vaccine purposes. Pharm Res 2007; 24:1870–1882.

    Article  CAS  PubMed  Google Scholar 

  431. Buonaguro L, Buonaguro FM, Tornesello ML et al. High efficient production of Pr55(gag) virus-like particles expressing multiple HIV-1 epitopes, including a gp120 protein derived from an Ugandan HIV-1 isolate of subtype A. Antiviral Res 2001; 49:35–47.

    Article  CAS  PubMed  Google Scholar 

  432. Gheysen D, Jacobs E, de Foresta F et al. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell 1989; 59:103–112.

    Article  CAS  PubMed  Google Scholar 

  433. Young KR, McBurney SP, Karkhanis LU et al. Virus-like particles: designing an effective AIDS vaccine. Methods 2006; 40:98–117.

    Article  CAS  PubMed  Google Scholar 

  434. McBurney SP, Young KR, Nwaigwe CI et al. Lentivirus-like particles without reverse transcriptase elicit efficient immune responses. Curr HIV Res 2006; 4:475–484.

    Article  CAS  PubMed  Google Scholar 

  435. Wagner R, Deml L, Notka F et al. Safety and immunogenicity of recombinant human immunodeficiency virus-like particles in rodents and rhesus macaques. Intervirology 1996; 39:93–103.

    CAS  PubMed  Google Scholar 

  436. Sailaja G, Skountzou I, Quan FS et al. Human immunodeficiency virus-like particles activate multiple types of immune cells. Virology 2007; 362:331–341.

    Article  CAS  PubMed  Google Scholar 

  437. Doan LX, Li M, Chen C et al. Virus-like particles as HIV-1 vaccines. Rev Med Virol 2005; 15:75–88.

    Article  PubMed  Google Scholar 

  438. Buonaguro L, Racioppi L, Tornesello ML et al. Induction of neutralizing antibodies and cytotoxic T-lymphocytes in Balb/c mice immunized with virus-like particles presenting a gp120 molecule from a HIV-1 isolate of clade A. Antiviral Res 2002; 54:189–201.

    Article  CAS  PubMed  Google Scholar 

  439. Buonaguro L, Visciano ML, Tornesello ML et al. Induction of systemic and mucosal cross-clade neutralizing antibodies in BALB/c mice immunized with human immunodeficiency virus type 1 clade A virus-like particles administered by different routes of inoculation. J Virol 2005; 79:7059–7067.

    Article  CAS  PubMed  Google Scholar 

  440. Schroder U, Svenson SB. Nasal and parenteral immunizations with diphtheria toxoid using monoglyceride/fatty acid lipid suspensions as adjuvants. Vaccine 1999; 17:2096–2103.

    Article  CAS  PubMed  Google Scholar 

  441. Buonaguro L, Devito C, Tornesello ML et al. DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity. Vaccine 2007; 25:5968–5977.

    Article  CAS  PubMed  Google Scholar 

  442. Karpenko LI, Ilyichev AA, Eroshkin AM et al. Combined virus-like particle-based polyepitope DNA/ protein HIV-1 vaccine design, immunogenicity and toxicity studies. Vaccine 2007; 25:4312–4323.

    Article  CAS  PubMed  Google Scholar 

  443. Paliard X, Liu Y, Wagner R et al. Priming of strong, broad and long-lived HIV type 1 p55gag-specific CD8+ cytotoxic T-cells after administration of a virus-like particle vaccine in rhesus macaques. AIDS Res Hum Retroviruses 2000; 16:273–282.

    Article  CAS  PubMed  Google Scholar 

  444. Adams SE, Dawson KM, Gull K et al. The expression of hybrid HIV:Ty virus-like particles in yeast. Nature 1987; 329:68–70.

    Article  CAS  PubMed  Google Scholar 

  445. Lindenburg CE, Stolte I, Langendam MW et al. Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty virus-like particles on HIV-1 disease progression. Vaccine 2002; 20:2343–2347.

    Article  CAS  PubMed  Google Scholar 

  446. Smith D, Hales G, Roth N et al. A randomized trial of nelfinavir, ritonavir, or delavirdine in combination with saquinavir-SGC and stavudine in treatment-experienced HIV-1-infected patients. HIV Clin Trials 2001; 2:97–107.

    Article  CAS  PubMed  Google Scholar 

  447. Nabel GJ. HIV vaccine strategies. Vaccine 2002; 20:1945–1947.

    Article  CAS  PubMed  Google Scholar 

  448. Amara RR, Villinger F, Altman JD et al. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Vaccine 2002; 20:1949–1955.

    Article  CAS  PubMed  Google Scholar 

  449. Goepfert P, Hay C, Frey S et al. HIV-1 DNA prime followed by recombinant MVA boost is well tolerated and immunogenic when administered to healthy HIV-1 seronegative adults in HVTN 065. (Poster 0A02-04, oral presentation, AIDS VAccine Conference, Seattle, Washington-USA; 2007), 2007.

    Google Scholar 

  450. Mwau M, Cebere I, Sutton J et al. A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans. J Gen Virol 2004; 85:911–919.

    Article  CAS  PubMed  Google Scholar 

  451. Levy JA. The importance of the innate immune system in controlling HIV infection and disease. Trends Immunol 2001; 22:312–316.

    Article  CAS  PubMed  Google Scholar 

  452. Goff SP. Retrovirus restriction factors. Mol Cell 2004; 16:849–859.

    Article  CAS  PubMed  Google Scholar 

  453. Koup RA, Safrit JT, Cao Y et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 1994; 68:4650–4655.

    CAS  PubMed  Google Scholar 

  454. Musey L, Hughes J, Schacker T et al. Cytotoxic-T-cell responses, viral load and disease progression in early human immunodeficiency virus type 1 infection. N Engl J Med 1997; 337:1267–1274.

    Article  CAS  PubMed  Google Scholar 

  455. Yasutomi Y, Reimann KA, Lord CI et al. Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys. J Virol 1993; 67:1707–1711.

    CAS  PubMed  Google Scholar 

  456. Jin X, Bauer DE, Tuttleton SE et al. Dramatic rise in plasma viremia after CD8(+) T-cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 1999; 189:991–998.

    Article  CAS  PubMed  Google Scholar 

  457. Schmitz JE, Kuroda MJ, Santra S et al. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 1999; 283:857–860.

    Article  CAS  PubMed  Google Scholar 

  458. Schmitz JE, Johnson RP, McClure HM et al. Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques. J Virol 2005; 79:8131–8141.

    Article  CAS  PubMed  Google Scholar 

  459. Miller CJ, Genesca M, Abel K et al. Antiviral antibodies are necessary for control of simian immunodeficiency virus replication. J Virol 2007; 81:5024–5035.

    Article  CAS  PubMed  Google Scholar 

  460. Schmitz JE, Kuroda MJ, Santra S et al. Effect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus. J Virol 2003; 77:2165–2173.

    Article  CAS  PubMed  Google Scholar 

  461. Dittmer U, Brooks DM, Hasenkrug KJ. Requirement for multiple lymphocyte subsets in protection by a live attenuated vaccine against retroviral infection. Nat Med 1999; 5:189–193.

    Article  CAS  PubMed  Google Scholar 

  462. Mao H, Lafont BA, Igarashi T et al. CD8+ and CD20+ lymphocytes cooperate to control acute simian immunodeficiency virus/human immunodeficiency virus chimeric virus infections in rhesus monkeys: modulation by major histocompatibility complex genotype. J Virol 2005; 79:14887–14898.

    Article  CAS  PubMed  Google Scholar 

  463. Qin Z, Richter G, Schuler T et al. B-cells inhibit induction of T-cell-dependent tumor immunity. Nat Med 1998; 4:627–630.

    Article  CAS  PubMed  Google Scholar 

  464. Recher M, Lang KS, Hunziker L et al. Deliberate removal of T-cell help improves virus-neutralizing antibody production. Nat Immunol 2004; 5:934–942.

    Article  CAS  PubMed  Google Scholar 

  465. Stager S, Alexander J, Kirby AC et al. Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses. Nat Med 2003; 9:1287–1292.

    Article  PubMed  CAS  Google Scholar 

  466. Zinkernagel RM. Immunity, immunopathology and vaccines against HIV? Vaccine 2002; 20:1913–1917.

    Article  CAS  PubMed  Google Scholar 

  467. Guy B. The perfect mix: recent progress in adjuvant research Nat Rev Microbiol 2007; 5:505–517.

    Article  CAS  PubMed  Google Scholar 

  468. Klausner RD, Fauci AS, Corey L et al. Medicine. The need for a global HIV vaccine enterprise. Science 2003; 300:2036–2039.

    Article  CAS  PubMed  Google Scholar 

  469. Ioannidis JP, Rosenberg PS, Goedert JJ et al. Effects of CCR5-Delta32, CCR2-64I and SDF-1 3’A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med 2001; 135:782–795.

    CAS  PubMed  Google Scholar 

  470. Martin MP, Gao X, Lee JH et al. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 2002; 31:429–434.

    CAS  PubMed  Google Scholar 

  471. Lopalco L, Barassi C, Pastori C et al. CCR5-reactive antibodies in seronegative partners of HIV-seropositive individuals down-modulate surface CCR5 in vivo and neutralize the infectivity of R5 strains of HIV-1 in vitro. J Immunol 2000; 164:3426–3433.

    CAS  PubMed  Google Scholar 

  472. Pastori C, Weiser B, Barassi C et al. Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression. Blood 2006; 107:4825–4833.

    Article  CAS  PubMed  Google Scholar 

  473. Belec L, Ghys PD, Hocini H et al. Cervicovaginal secretory antibodies to human immunodeficiency virus type 1 (HIV-1) that block viral transcytosis through tight epithelial barriers in, highly exposed HIV-1-seronegative African women. J Infect Dis 2001; 184:1412–1422.

    Article  CAS  PubMed  Google Scholar 

  474. O’Connor GM, Holmes A, Mulcahy F et al. Natural Killer cells from long-term nonprogressor HIV patients are characterized by altered phenotype and function. Clin Immunol 2007; 124:277–283.

    Article  PubMed  CAS  Google Scholar 

  475. Broliden K, Hinkula J, Devito C et al. Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG seronegative female sex workers. Immunol Lett 2001; 79:29–36.

    Article  CAS  PubMed  Google Scholar 

  476. Kannanganat S, Kapogiannis BG, Ibegbu C et al. Human immunodeficiency virus type 1 controllers but not noncontrollers maintain CD4 T-cells coexpressing three cytokines. J Virol 2007; 81:12071–12076.

    Article  CAS  PubMed  Google Scholar 

  477. Rezza G, Titti F, Pezzotti P et al. Anti-nef antibodies and other predictors of disease progression in HIV-1 seropositive injecting drug users. J Biol Regul Homeost Agents 1992; 6:15–20.

    CAS  PubMed  Google Scholar 

  478. Inwoley A, Recordon-Pinson P, Dupuis M et al. Cross-clade conservation of HIV type 1 Nef immunodominant regions recognized by CD8+ T-cells of HIV type 1 CRF02_AG-infected Ivorian (West Africa). AIDS Res Hum Retroviruses 2005; 21:620–628.

    Article  CAS  PubMed  Google Scholar 

  479. Wilson CC, McKinney D, Anders M et al. Development of a DNA vaccine designed to induce cytotoxic T-lymphocyte responses to multiple conserved epitopes in HIV-1. J Immunol 2003; 171:5611–5623.

    CAS  PubMed  Google Scholar 

  480. Brave A, Ljungberg K, Wahren B et al. Vaccine delivery methods using viral vectors. Mol Pharm 2007; 4:18–32.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Barbara Ensoli .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Cafaro, A., Macchia, I., Maggiorella, M.T., Titti, F., Ensoli, B. (2009). Innovative Approaches to Develop Prophylactic and Therapeutic Vaccines against HIV/AIDS. In: Guzmán, C.A., Feuerstein, G.Z. (eds) Pharmaceutical Biotechnology. Advances in Experimental Medicine and Biology, vol 655. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1132-2_14

Download citation

Publish with us

Policies and ethics