title: Generation and characterization of six single VP4 gene substitution reassortant rotavirus vaccine candidates: each bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU18006 or bovine rotavirus UK.
abstract: The global disease burden of rotavirus diarrhea in infants and young children has stimulated interest in the biological and clinical characteristics of these agents, leading to intensive efforts to develop a vaccine. A rhesus rotavirus (RRV)-based quadrivalent vaccine ("RotaShield") was licensed and administered to about 1 million infants and found to be highly effective. However, it was withdrawn because of a link with intussusception. This vaccine was developed according to a modified "Jennerian" approach in which one of the two major outer capsid proteins (VP7) shares neutralization specificity with one of the four epidemiologically important human rotavirus serotypes. The other outer capsid protein (VP4) is derived solely from RRV and is distinct from the VP4 of the four human rotavirus serotypes of epidemiologic importance. In an effort to further increase the immunogenicity of the existing VP7-based RRV quadrivalent vaccine, we generated three single VP4 gene substitution reassortant rotavirus candidate vaccines, each of which bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] specificity while the remaining 10 genes are derived from the rhesus rotavirus. By incorporating one or two of these strains into the quadrivalent vaccine, a pentavalent or hexavalent RRV-based vaccine could be formulated thus providing antigenic coverage not only for VP7 serotype 1, 2, 3 and 4 but also for VP4 serotype 1A[8] or 1B[4], thus possibly augmenting its immunogenicity. Similarly, three single VP4 gene (P1A[8] or P1B[4]) substitution reassortants have also been generated in a background of 10 bovine (UK) rotavirus genes for addition to a second generation UK-based quadrivalent vaccine.
authors.affiliation: Epidemiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50, Room 6308, 50 South Drive MSC 8026, Bethesda, MD 20892-8026, USA. thoshino@niaid.nih.gov
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Jones
authors.forename: Robert M
authors.initials: RM
authors.lastname: Chanock
authors.forename: Albert Z
authors.initials: AZ
authors.lastname: Kapikian
mesh_terms: D000818:Animals; D000956:Antigens, Viral; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology; D002417:Cattle / Q000821:virology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006168:Guinea Pigs; D007114:Immunization; D008253:Macaca mulatta / Q000821:virology*; D016865:Reassortant Viruses / Q000276:immunology*; D012401:Rotavirus / Q000145:classification* / Q000235:genetics; D022243:Rotavirus Vaccines / Q000276:immunology*; D012703:Serotyping
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D022243:Rotavirus Vaccines; C060339:VP4 protein, Rotavirus; C050779:VP7 protein, Rotavirus