Rational design of a live-attenuated eastern equine encephalitis virus vaccine through informed mutation of virulence determinants.

ABSTRACT: Live attenuated vaccines (LAVs), if sufficiently safe, provide the most potent and durable anti-pathogen responses in vaccinees with single immunizations commonly yielding lifelong immunity. Historically, viral LAVs were derived by blind passage of virulent strains in cultured cells resulting in adaptation to culture and a loss of fitness and disease-causing potential in vivo. Mutations associated with these phenomena have been identified but rarely have specific attenuation mechanisms been ascribed, thereby limiting understanding of the attenuating characteristics of the LAV strain and applicability of the attenuation mechanism to other vaccines. Furthermore, the attenuated phenotype is often associated with single nucleotide changes in the viral genome, which can easily revert to the vir

SUBMITTER: Trobaugh DW 

PROVIDER: S-EPMC6386422 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature