Construction and characterization of rhesus monkey rotavirus (MMU18006)- or bovine rotavirus (UK)-based serotype G5, G8, G9 or G10 single VP7 gene substitution reassortant candidate vaccines

Abstract

Group A rotaviruses are the single most important etiologic agents of severe diarrhea of infants and young children worldwide and have been estimated to be responsible for approximately 650,000–800,000 deaths annually in children <5-year-old in the developing countries. Thus, the development of a safe and effective rotavirus vaccine has been a global public health goal. Epidemiologic surveillance of rotavirus VP7 (G) serotypes–genotypes conducted in various populations throughout the world has repeatedly shown that approximately 90% of the typeable rotavirus isolates belong to G1–G4. For these reasons, we have developed a rhesus rotavirus (RRV)-based or bovine rotavirus (UK)-based quadrivalent vaccine which is designed to provide antigenic coverage for G1–G4. More recently, G serotypes–genotypes other than G1–G4, including G5, G8–G10, have been detected in various parts of the world. Although the occurrence of such uncommon G types, except for G9, has been focal, still, in order to “be ready and prepared”, we have constructed and characterized eight additional reassortant rotavirus vaccines, each of which bears a single human or bovine VP7 gene encoding G serotype 5, 8, 9 or 10 specificity and the remaining 10 genes of RRV strain MMU18006 or bovine rotavirus strain UK. These candidate vaccines could be evaluated singly in special populations or in combination with a RRV- or an UK-based quadrivalent vaccine to broaden its G serotype specificity.