title: A hexavalent human rotavirus-bovine rotavirus (UK) reassortant vaccine designed for use in developing countries and delivered in a schedule with the potential to eliminate the risk of intussusception.
abstract: There is an urgent need for a rotavirus vaccine, because up to 592,000 infants and young children <5 years old die each year from rotavirus diarrhea, predominantly in the developing countries. We have developed a tetravalent human-bovine rotavirus (UK) reassortant vaccine with VP7 (G) specificity for serotypes 1, 2, 3, and 4, which has been shown to be safe, immunogenic, and effective in preventing severe rotavirus diarrhea. However, because of the emergence of VP7 (G) serotype 9 as an epidemiologically important serotype and the importance of VP7 (G) serotype 8 in focal areas, we are planning to add human-bovine (UK) reassortants with G8 and G9 specificity to the tetravalent vaccine, thereby formulating a "designed" hexavalent vaccine for universal use. In addition, we propose that the vaccine be administered orally in a 2-dose schedule, with the first dose given at 0-4 weeks of age and the second dose given at 4-8 weeks of age, when infants are relatively refractory to developing intussusception, thereby avoiding the age period when naturally occurring intussusception is most prevalent (i.e., ages 3-4 months through age 9 months). In this way, there may be the potential to eliminate or at least significantly decrease the risk of intussusception associated with rotavirus vaccination.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. akapikian@niaid.nih.gov
authors.forename: Albert Z
authors.initials: AZ
authors.lastname: Kapikian
authors.forename: Lone
authors.initials: L
authors.lastname: Simonsen
authors.forename: Timo
authors.initials: T
authors.lastname: Vesikari
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Hoshino
authors.forename: David M
authors.initials: DM
authors.lastname: Morens
authors.forename: Robert M
authors.initials: RM
authors.lastname: Chanock
authors.forename: John R
authors.initials: JR
authors.lastname: La Montagne
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
mesh_terms: D000284:Administration, Oral; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D002986:Clinical Trials as Topic; D003906:Developing Countries; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007443:Intussusception / Q000209:etiology*; D016865:Reassortant Viruses / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D013045:Species Specificity
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D022243:Rotavirus Vaccines; C050779:VP7 protein, Rotavirus