title: Homotypic and heterotypic serum neutralizing antibody response to rotavirus proteins following natural primary infection and reinfection in children.
abstract: Worldwide trials of rotavirus vaccines are currently in progress, but the basis of cross-reactive immunity between rotavirus serotypes is yet to be elucidated. The involvement of the outer capsid proteins, VP7 and VP4, in the production of cross-reactive neutralizing antibody (N-Ab) is unclear, and may be important for the success of animal rotavirus-based candidate vaccines that lack a VP4 of human rotavirus origin. In this study, VP7- and VP4-specific N-Ab was assayed in sera from children experiencing primary (27 children) and/or secondary (14 children) rotavirus infections using human-animal reassortant strains. These reassortants contained genes encoding the major G- and P-types found in human infection, including G1, 2, 3, and 4; or P1A[8], 1B[4], and 2[6]. After primary infection, the N-Ab response to VP7 was generally serotype-specific, whereas the response to VP4 was heterotypic. After reinfection (with the same or different serotypes) there was a significant increase (P=0.0313) in the number of VP7 serotypes seroconverted against with no broadening of cross-reactivity to VP4. Increases in homotypic N-Ab titer, following both primary and secondary infection, were greater against VP7 than VP4, with the seroconversion against VP7 being significantly greater upon reinfection than following primary infection (P=0.0280). In summary, heterotypic N-Ab produced following primary infection appears to be primarily against VP4. However, upon reinfection, VP7 becomes increasingly immunodominant both in terms of cross-reactive N-Ab production and increases in N-Ab titer.
authors.affiliation: Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Victoria, Australia. gastro@cryptic.rch.unimelb.edu.au
authors.forename: R J
authors.initials: RJ
authors.lastname: Gorrell
authors.forename: R F
authors.initials: RF
authors.lastname: Bishop
mesh_terms: D000910:Antibodies, Heterophile / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000956:Antigens, Viral / Q000097:blood / Q000276:immunology; D002213:Capsid / Q000097:blood / Q000276:immunology*; D036022:Capsid Proteins; D002675:Child, Preschool; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D009500:Neutralization Tests; D011159:Population Surveillance; D016865:Reassortant Viruses / Q000276:immunology; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000097:blood / Q000276:immunology*
chemical_list: D000910:Antibodies, Heterophile; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D006389:Hemagglutinins, Viral; C060339:VP4 protein, Rotavirus; C050779:VP7 protein, Rotavirus