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Using Immunoinformatics and Structural Approaches to Design a Novel HHV8 Vaccine

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Abstract

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) has caused infection in different parts of the world, especially in Africa, the Middle East, and the Mediterranean. HHV8 is a gamma-2 class herpesvirus and its genome contains 26 open reading frames. K1 is a highly variable glycoprotein and can be used as a vaccine candidate. The aim of this study was to design a new vaccine by using immunoinformatics analysis and adding approved adjuvants. In this study, several computational programs were employed to define the most capable region in K1-based immunologic properties; also, different possible adjuvants and universal T-helper agonists were added to the new construct. The construct was examined to define the 3D structure, physicochemical properties and immunologic features. In addition, docking analysis was done to define the ability of the new construct to attach to mTLR. A region (155–170) was selected to be used in the new proposed vaccine; in addition, two TLR agonist adjuvants and two universal T-helpers were added to boost the immune response. Analysis of the new construct showed that the designed protein was able to be used as a vaccine and be expressed in the host. Moreover, the high energy value in docking analysis showed the high ability of this vaccine to induce immune system. The designed vaccine is expected to be capable of generating humoral and cellular responses that are crucial to protect against HHV8 as well as the vaccine has appropriate physicochemical properties and acceptable stability in different host cells.

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References

  • Betsem E, Cassar O, Afonso PV, Fontanet A, Froment A, Gessain A (2014) Epidemiology and genetic variability of HHV-8/KSHV in Pygmy and Bantu populations in Cameroon. PLoS Negl Trop Dis 8:e2851

    Article  Google Scholar 

  • Borhani K, Bamdad T, Hashempour T (2017) Low dose of lenalidomide enhances NK cell activity: possible implication as an adjuvant. Iran J Immunol 14:151–158

    PubMed  Google Scholar 

  • Carbone A, Gloghini A, Vaccher E, Marchetti G, Gaidano G, Tirelli U (2005) KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects. Report of two cases with anaplastic large cell morphology and plasmablastic immunophenotype. J Clin Pathol 58:1039–1045

    Article  CAS  Google Scholar 

  • Dehghani B, Rasooli I, Gargari SLM, Nadooshan MRJ, Owlia P, Nazarian S (2013) Immunogenicity of Salmonella enterica serovar Enteritidis virulence protein, InvH, and cross-reactivity of its antisera with Salmonella strains. Microbiol Res 168:84–90

    Article  CAS  Google Scholar 

  • Dehghani B, Rasooli I, Jalali-Nadoushan M, Owlia P, Rasooli Z (2014) Immunoprotectivity of Salmonella enterica serovar Enteritidis virulence protein, InvH, against Salmonella typhi. Iran J Basic Med Sci 17:560

    PubMed  PubMed Central  Google Scholar 

  • Dehghani B, Ghasabi F, Hashempoor T, Joulaei H, Hasanshahi Z, Halaji M, Chatrabnous N, Mousavi Z, Moayedi J (2017) Functional and structural characterization of Ebola virus glycoprotein (1976–2015)—An in silico study. Int J Biomath 10:1750108

    Article  Google Scholar 

  • Duthie MS, Windish HP, Fox CB, Steven GR (2011) Use of defined TLR ligands as adjuvants within human vaccines. Immunol Rev 239:178–196

    Article  CAS  Google Scholar 

  • Edelman DC (2005) Human herpesvirus 8: a novel human pathogen. Virol J 2:78

    Article  Google Scholar 

  • Etta E, Alayande D, Mavhandu-Ramarumo L, Gachara G, Bessong P (2018) HHV-8 seroprevalence and genotype distribution in Africa, 1998–2017: a systematic review. Viruses 10:458

    Article  Google Scholar 

  • Farhadi T, Karimi Z, Ghasemi Y, Nezafat N, Hemmati S, Erfani N (2015) Production of a novel multi-epitope vaccine based on outer membrane proteins of Klebsiella pneumoniae. Trends Pharm Sci 1:167–172

    CAS  Google Scholar 

  • Fraser CC, David H, Altreuter P, Ilyinskii L, Pittet RA, LaMothe M, Keegan, Johnston L, Kishimoto TK (2014) Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates. Vaccine 32:2896–2903

    Article  CAS  Google Scholar 

  • Giannini SL, Hanon PE, Moris M, Van Mechelen S, Morel F, Dessy MA, Fourneau B, Colau J, Suzich J, Losonksy G (2006) Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine 24:5937–5949

    Article  CAS  Google Scholar 

  • Hayashi F, Smith KD, Ozinsky A, Thomas R, Hawn CY, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:1099

    Article  CAS  Google Scholar 

  • Jiang RT, Schellenbacher C, Chackerian B, Richard BSR (2016) Progress and prospects for L2-based human papillomavirus vaccines. Expert Rev Vaccines 15:853–862

    Article  CAS  Google Scholar 

  • Kalnin K, Tibbitts T, Stegalkina Y, Yan S, Shen L, Costa V, Sabharwal R, Anderson SF, Day PM, Christensen N (2014) Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes. Vaccine 32:3540–3547

    Article  CAS  Google Scholar 

  • Kasturi SP, Skountzou I, Albrecht RA, Koutsonanos D, Hua T, Nakaya HI, Ravindran R, Stewart S, Alam M, Kwissa M (2011) Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470:543

    Article  CAS  Google Scholar 

  • Lu J, Sun PD (2012) The structure of the TLR5-flagellin complex: a new mode of pathogen detection, conserved receptor dimerization for signaling. Sci Signal 5:pe11–pe11

    Article  Google Scholar 

  • Marston HD, Folkers GK, Morens DM, Anthony SF (2014) Emerging viral diseases: confronting threats with new technologies. Sci Transl Med 6:253ps10–53ps10

    Article  Google Scholar 

  • Masa S-R, Lando R, Sarid R (2008) Transcriptional regulation of the open reading frame 35 encoded by Kaposi’s sarcoma-associated herpesvirus. Virology 371:14–31

    Article  CAS  Google Scholar 

  • Mizel SB, John TB (2010) Flagellin as an adjuvant: cellular mechanisms and potential. J Immunol 185:5677–5682

    Article  CAS  Google Scholar 

  • Moattari A, Dehghani B, Khodadad N, Forogh, Tavakoli (2015) In silico functional and structural characterization of H1N1 influenza a viruses hemagglutinin, 2010–2013, Shiraz, Iran. Acta Biotheoretica 63:183–202

    Article  Google Scholar 

  • Mori J, Vranac T, Smrekar B, Černilec M, Šerbec VC, Horvat S, Ihan A, Benčina M, Jerala R (2012) Chimeric flagellin as the self-adjuvanting antigen for the activation of immune response against Helicobacter pylori, Vaccine, 30:5856–5863

    Article  CAS  Google Scholar 

  • Mui U, Ngoc CT, Haley R, Vangipuram, Stephen KT (2018) Human Oncoviruses: mucocutaneous manifestations, pathogenesis, therapeutics, and prevention (Part II: hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus). J Am Acad Dermatol. https://doi.org/10.1016/j.jaad.2018.10.072

    Article  PubMed  Google Scholar 

  • Negahdaripour M, Eslami M, Nezafat N, Hajighahramani N, Ghoshoon MB, Shoolian E, Dehshahri A, Erfani N, Morowvat MH, Ghasemi Y (2017) A novel HPV prophylactic peptide vaccine, designed by immunoinformatics and structural vaccinology approaches. Infect Genet Evol 54:402–416

    Article  CAS  Google Scholar 

  • Ouyang X, Zeng Y, Fu B, Wang X, Chen W, Fang Y, Luo M, Wang L (2014) Genotypic analysis of Kaposi’s sarcoma-associated herpesvirus from patients with Kaposi’s sarcoma in Xinjiang, China. Viruses 6:4800–4810

    Article  Google Scholar 

  • Prakash O, Swamy OR, Peng X, Tang Z-Y, Li L, Larson JE, Cohen JC, Gill J, Farr G, Wang S (2005) Activation of Src kinase Lyn by the Kaposi sarcoma-associated herpesvirus K1 protein: implications for lymphomagenesis. Blood 105:3987–9394

    Article  CAS  Google Scholar 

  • Pyakurel P, Pak F, Mwakigonja AR, Kaaya E, Biberfeld P (2007) KSHV/HHV-8 and HIV infection in Kaposi’s sarcoma development. Infect Agents Cancer 2:4

    Article  Google Scholar 

  • Ramón A, Señorale M, Marín M (2014) Inclusion bodies: not that bad… Front Microbiol 5:56

  • Rumbo M, Nempont C, Kraehenbuhl J-P, Jean-Claude Sirard (2006) Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5. FEBS Lett 580:2976–2984

    Article  CAS  Google Scholar 

  • Shanmugam A, Rajoria S, George AL, Mittelman A, Suriano R, Raj KT (2012) Synthetic Toll like receptor-4 (TLR-4) agonist peptides as a novel class of adjuvants. PloS ONE 7:e30839

    Article  CAS  Google Scholar 

  • Song WS, Yoon S-i (2014) Crystal structure of FliC flagellin from Pseudomonas aeruginosa and its implication in TLR5 binding and formation of the flagellar filament. Biochem Biophys Res Commun 444:109–115

    Article  CAS  Google Scholar 

  • Song WS, Jeon YJ, Namgung B, Hong M, Yoon Sl (2017) A conserved TLR5 binding and activation hot spot on flagellin. Sci Rep 7:40878

    Article  CAS  Google Scholar 

  • Sra KK, Michelle Babb-Tarbox S, Aboutalebi P, Rady GL, Shipley DD, Dao, Stephen KT (2005) Molecular diagnosis of cutaneous diseases. Arch Dermatol 141:225–241

    Article  CAS  Google Scholar 

  • Tarahomjoo S (2014) Utilizing bacterial flagellins against infectious diseases and cancers. Antonie Van Leeuwenhoek 105:275–288

    Article  CAS  Google Scholar 

  • Wang L, Wakisaka N, Tomlinson CC, DeWire SM, Krall S, Pagano JS, Damania B (2004) The Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) K1 protein induces expression of angiogenic and invasion factors. Cancer Res 64:2774–2781

    Article  CAS  Google Scholar 

  • Yoon S, Kurnasov O, Natarajan V, Hong M, Gudkov AV, Osterman AL, Ian AW (2012) Structural basis of TLR5-flagellin recognition and signaling. Science 335:859–864

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by Grant no. 16304 from the Research Council of Shiraz University of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. The authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran and also Center for Development of Clinical Research of Nemazee Hospital and Dr. Nasrin Shokrpour for editorial assistance. We thank Dr.Hassan Joulaei, Mr.Javad Moayedi for their scientific comments and support.‏‏

Funding

This study was funded by Shiraz University of Medical Sciences (Grant No. 16304).

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Correspondence to Tayebeh Hashempour.

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Author Behzad Dehghani declares that he has no conflict of interest. Author Tayebeh Hashempoor declares that she has no conflict of interest. Hassan Joulaei declares that he has no conflict of interest Author Zahra Hasanshahi declares that she has no conflict of interest.

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Dehghani, B., Hashempour, T. & Hasanshahi, Z. Using Immunoinformatics and Structural Approaches to Design a Novel HHV8 Vaccine. Int J Pept Res Ther 26, 321–331 (2020). https://doi.org/10.1007/s10989-019-09839-x

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  • DOI: https://doi.org/10.1007/s10989-019-09839-x

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