Elsevier

Vaccine

Volume 24, Issue 15, 5 April 2006, Pages 2718-2731
Vaccine

Review
Immunity and correlates of protection for rotavirus vaccines

https://doi.org/10.1016/j.vaccine.2005.12.048Get rights and content

Abstract

Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The tremendous global incidence of rotavirus gastroenteritis, especially in developing countries, emphasizes the need for vaccines to prevent associated morbidity and mortality. However, immunity to rotavirus is not completely understood. At this time, total serum RV IgA, measured shortly after infection, appears to be the best marker of protection against rotavirus. This review describes the current understanding of rotavirus immunity, including mechanisms of protection against rotavirus from selected animal models, and correlates of protection associated with natural infection or vaccination from humans.

Introduction

Since their discovery in 1973 [1] rotaviruses (RVs) have been identified as the most common cause of severe, dehydrating diarrhea in children worldwide [2], [3]. RV immunity is not completely understood and issues like the relative role of serotype specific versus heterotypic immunity are controversial [4]. The role of serum antibodies in human immunity to RV has recently been reviewed [5]. Here, we will briefly review aspects of viral pathogenesis, serotype classification and epidemiology that shed light on RV immunity, followed by a discussion of the mechanisms of protection against RV in selected animal models (with emphasis on our results from the adult mouse model), and the correlates of protection associated with natural infection or vaccination in humans. We will emphasize total serum RV IgA and RV serum neutralizing antibodies as possible correlates of protection against disease.

Section snippets

Pathogenesis, serotype classification and epidemiology

RVs have characteristics that make them highly infectious pathogens very well adapted to their host (Table 1). RV belong to a large group of pathogens that will never be eradicated because they do not generate sterilizing immunity and because RV can infect animal hosts. Thus, reasonable goals of vaccination are probably to decrease or eliminate severe disease in children but not to prevent infection. The physiopathological mechanisms of RV induced diarrhea are multiple and not yet completely

Mechanisms of protection in animal models

Animal models have been instrumental for our understanding of immunity to RV. A comprehensive review of the literature of this subject is not intended, and with few exceptions, we will only refer to selected papers of the murine and the neonatal gnotobiotic pig models, that have been the most frequently used models. Each animal model offers certain advantages and disadvantages. For example, the adult mouse model is an infection only model [24], while in the pig model, protection against

Future studies to better understand immunity to RV and obtain better correlates of protection

From the above discussion, it is clear that we need a better understanding of immunity to RV in children. The nature of human cross-reactive antibodies against VP4, or VP7, is poorly understood. A recent study of human monoclonal neutralizing antibodies showed that cross-reactive neutralization epitopes recognized by humans may be distinct from those of mice. Moreover, the two human monoclonal antibodies evaluated were cross-reactive for at least two P genotypes [51]. Hence, humans, like mice,

Conclusions

  • a.

    Intestinal IgA is probably the most important mechanism for long-term protection against RV.

  • b.

    Total serum RV IgA measured shortly after infection generally reflects intestinal IgA levels, and may be the best (but imperfect) available marker that correlates with protection against RV. Total serum RV IgA can probably be used as a correlate of protection for many of the vaccines in development and in use.

  • c.

    Correlates of protection after vaccination may vary depending on the type (homologous versus

Acknowledgments

This work was supported by funds from the Pontificia Universidad Javeriana, Colciencias Grants 1203-04-12638 and 1203-04-16466, FIRCA Grants TWO5647-01 and TW005647-04 and by NIH Grants R01 AI21362-20 and Digestive Disease Center Grant DK56339 and a VA Merit Review Grant.

References (128)

  • T. Vesikari

    Clinical trials of live oral rotavirus vaccines: the Finnish experience

    Vaccine

    (1993)
  • C.F. Lanata et al.

    Immunogenicity, safety and protective efficacy of one dose of the rhesus rotavirus vaccine and serotype 1 and 2 human–rhesus rotavirus reassortants in children from Lima, Peru

    Vaccine

    (1996)
  • M. Santosham et al.

    Efficacy and safety of high-dose rhesus–human reassortant rotavirus vaccine in Native American populations

    J Pediatr

    (1997)
  • R.L. Ward et al.

    Lack of correlation between serum rotavirus antibody titers and protection following vaccination with reassortant RRV vaccines. US Rotavirus Vaccine Efficacy Group

    Vaccine

    (1995)
  • T. Vesikari et al.

    Protection of infants against rotavirus diarrhoea by RIT 4237 attenuated bovine rotavirus strain vaccine

    Lancet

    (1984)
  • T. Vesikari et al.

    Clinical efficacy of the RIT 4237 live attenuated bovine rotavirus vaccine in infants vaccinated before a rotavirus epidemic

    J Pediatr

    (1985)
  • U.D. Parashar et al.

    Global illness and deaths caused by rotavirus disease in children

    Emerg Infect Dis

    (2003)
  • Organization WH. State of the art of new vaccines: research and development. Geneva (Switzerland): WHO;...
  • Y. Hoshino et al.

    Rotavirus serotypes: classification and importance in epidemiology, immunity, and vaccine development

    J Health Popul Nutr

    (2000)
  • B. Jiang et al.

    The role of serum antibodies in the protection against rotavirus disease: an overview

    Clin Infect Dis

    (2002)
  • G.P. Davidson et al.

    Structural and functional abnormalities of the small intestine in infants and young children with rotavirus enteritis

    Acta Paediatr Scand

    (1979)
  • V.T. Kohler et al.

    Histologische befunde der Dunndarmschleimhaut bei rotavirus-infektionen im sauglings-und kleinkindalter (Histological findings in the small intestinal mucosa in children with rotavirus infection)

    Kinderarztl Prax

    (1990)
  • M.A. Franco et al.

    Rotaviruses

  • N. Santos et al.

    Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine

    Rev Med Virol

    (2004)
  • M. Gorziglia et al.

    Antigenic relationships among human rotaviruses as determined by outer capsid protein VP4

    Proc Natl Acad Sci USA

    (1990)
  • C.S. Diwakarla et al.

    Genetic and antigenic variation of capsid protein VP7 of serotype G1 human rotavirus isolates

    J Gen Virol

    (1999)
  • H.F. Clark et al.

    Assessment of the epidemic potential of a new strain of rotavirus associated with the novel G9 serotype which caused an outbreak in the United States for the first time in the 1995–1996 season

    J Clin Microbiol

    (2004)
  • M. Ramachandran et al.

    Lack of maternal antibodies to P serotypes may predispose neonates to infections with unusual rotavirus strains

    Clin Diagn Lab Immunol

    (1998)
  • T. Mikami et al.

    An outbreak of gastroenteritis during school trip caused by serotype G2 group A rotavirus

    J Med Virol

    (2004)
  • D.D. Griffin et al.

    Outbreaks of adult gastroenteritis traced to a single genotype of rotavirus

    J Infect Dis

    (2002)
  • H. Yan et al.

    Outbreak of acute gastroenteritis associated with group A rotavirus and genogroup I sapovirus among adults in a mental health care facility in Japan

    J Med Virol

    (2005)
  • F. Mota-Hernandez et al.

    Rotavirus diarrhea severity is related to the VP4 type in Mexican children

    J Clin Microbiol

    (2003)
  • C. Bern et al.

    Rotavirus diarrhea in Bangladeshi children: correlation of disease severity with serotypes

    J Clin Microbiol

    (1992)
  • O. Nakagomi et al.

    Molecular evidence for naturally occurring single VP7 gene substitution reassortant between human rotaviruses belonging to two different genogroups

    Arch Virol

    (1991)
  • T. Nakagomi et al.

    Genogroup characterization of reemerging serotype G9 human rotavirus strain 95H115 in comparison with earlier G9 and other human prototype strains

    Microbiol Immunol

    (2002)
  • M.A. Franco et al.

    Immunity to rotavirus infection in mice

    J Infect Dis

    (1999)
  • J. Mestecky et al.

    Mucosal immunoglobulins

  • J. McAleer et al.

    Antibody repertoire development in fetal and neonatal piglets. XI. The thymic B-cell repertoire develops independently from that in blood and mesenteric lymph nodes

    Immunology

    (2005)
  • L. Yuan et al.

    Systemic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease

    J Virol

    (1996)
  • K.R. Youngman et al.

    Correlation of tissue distribution, developmental phenotype, and intestinal homing receptor expression of antigen-specific B cells during the murine anti-rotavirus immune response

    J Immunol

    (2002)
  • M.S. Azevedo et al.

    Viremia and nasal and rectal shedding of rotavirus in gnotobiotic pigs inoculated with Wa human rotavirus

    J Virol

    (2005)
  • E. Chiappini et al.

    Viraemia is a common finding in immunocompetent children with rotavirus infection

    J Med Virol

    (2005)
  • M.B. Williams et al.

    The memory B cell subset that is responsible for the mucosal IgA response and humoral immunity to rotavirus expresses the mucosal homing receptor, α4β7

    J Immunol

    (1998)
  • J.P. Bouvet et al.

    Diversity of antibody-mediated immunity at the mucosal barrier

    Infect Immun

    (1999)
  • J.W. Burns et al.

    Protective effect of rotavirus VP6-specific IgA monoclonal antibodies that lack neutralizing activity

    Science

    (1996)
  • N. Feng et al.

    Inhibition of rotavirus replication by a non-neutralizing, rotavirus VP6-specific IgA mAb

    J Clin Invest

    (2002)
  • J.M. Ball et al.

    Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein

    Science

    (1996)
  • C.M. O’Neal et al.

    Protection of the villus epithelial cells of the small intestine from rotavirus infection does not require immunoglobulin A

    J Virol

    (2000)
  • N.A. Kuklin et al.

    Protective intestinal anti-rotavirus B cell immunity is dependent on α4β7 integrin expression but does not require IgA antibody production

    J Immun

    (2006)
  • L.E. Westerman et al.

    Serum IgG mediates mucosal immunity against rotavirus infection

    Proc Natl Acad Sci USA

    (2005)
  • Cited by (234)

    • Gastrointestinal Tract Infections: Viruses

      2022, Encyclopedia of Infection and Immunity
    View all citing articles on Scopus
    View full text