Mutations of two amino acids in VP5 mediate the attenuation of human rotavirus vaccine: evidence from <i>in vitro</i> and <i>in vivo</i> studies.

ABSTRACT: Various vaccines, like polio, measles, and rotavirus, have been developed by serial-passaging in cell culture. Live oral rotavirus vaccines have been shown to be generally safe, but mechanisms of attenuation are not known. We have used a new, entirely plasmid-based reverse genetics system to artificially generate the novel human rotavirus vaccine strain CDC-9 (G1P[8]) and analyze the effect of the mutations within the VP4 gene on adaptation in vitro and attenuation in vivo. We demonstrated that out of the 6 amino acid mutations that appeared after serial passaging in Vero cells, mutations of wild-type CDC-9 P11 at VP4 AA331 and AA385 each or in combination were associated with increased replication in vitro comparable to cell-culture adapted CDC-9 P45. Neonatal rats in

SUBMITTER: Bessey TK 

PROVIDER: S-EPMC12645992 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature