title: Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.
abstract: RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Clinical and Epidemiological virology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Heylen
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Clinical and Epidemiological virology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: Zeller
authors.affiliation: Vaccines-Clinical Research Department, Merck Research Laboratories, North Wales, PA 19454, United States of America.
authors.forename: Max
authors.initials: M
authors.lastname: Ciarlet
authors.affiliation: Vaccines-Clinical Research Department, Merck Research Laboratories, North Wales, PA 19454, United States of America.
authors.forename: Jody
authors.initials: J
authors.lastname: Lawrence
authors.affiliation: PATH, Seattle, WA, United States of America.
authors.forename: Duncan
authors.initials: D
authors.lastname: Steele
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Clinical and Epidemiological virology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Clinical and Epidemiological virology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Jelle
authors.initials: J
authors.lastname: Matthijnssens
mesh_terms: D000349:Africa / Q000453:epidemiology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002417:Cattle; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012401:Rotavirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D012400:Rotavirus Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D022243:Rotavirus Vaccines; D017361:Viral Nonstructural Proteins