title: Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi.
abstract: The human, G1P[8] rotavirus vaccine (Rotarix™) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix™) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or the DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains.
authors.affiliation: Division of Molecular Epidemiology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, and the Global Centre of Excellence, Nagasaki University, Nagasaki, Japan.
authors.forename: Toyoko
authors.initials: T
authors.lastname: Nakagomi
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagomi
authors.forename: Winifred
authors.initials: W
authors.lastname: Dove
authors.forename: Yen Hai
authors.initials: YH
authors.lastname: Doan
authors.forename: Desiree
authors.initials: D
authors.lastname: Witte
authors.forename: Bagrey
authors.initials: B
authors.lastname: Ngwira
authors.forename: Stacy
authors.initials: S
authors.lastname: Todd
authors.forename: A
authors.initials: A
authors.lastname: Duncan Steele
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Cunliffe
mesh_terms: D016000:Cluster Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005243:Feces / Q000821:virology; D005814:Genes, Viral; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008295:Malawi / Q000453:epidemiology; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012401:Rotavirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000453:epidemiology* / Q000517:prevention & control / Q000821:virology*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D017422:Sequence Analysis, DNA
chemical_list: D012367:RNA, Viral; D022243:Rotavirus Vaccines