Chimeric Chikungunya viruses are nonpathogenic in highly sensitive mouse models but efficiently induce a protective immune response
Chikungunya virus (CHIKV) is an important pathogen causing outbreaks of highly
debilitating and often chronic, arthralgic human disease. We have designed chimeric
alphaviruses encoding CHIKV-specific structural proteins but no structural or nonstructural
proteins capable of interfering with development of cellular antiviral response. These
chimeras demonstrate a highly attenuated phenotype in both immunocompetent and
immunocompromised (A129) mice. However, after a single vaccination, they induced …
debilitating and often chronic, arthralgic human disease. We have designed chimeric
alphaviruses encoding CHIKV-specific structural proteins but no structural or nonstructural
proteins capable of interfering with development of cellular antiviral response. These
chimeras demonstrate a highly attenuated phenotype in both immunocompetent and
immunocompromised (A129) mice. However, after a single vaccination, they induced …
Abstract
Chikungunya virus (CHIKV) is an important pathogen causing outbreaks of highly debilitating and often chronic, arthralgic human disease. We have designed chimeric alphaviruses encoding CHIKV-specific structural proteins but no structural or nonstructural proteins capable of interfering with development of cellular antiviral response. These chimeras demonstrate a highly attenuated phenotype in both immunocompetent and immunocompromised (A129) mice. However, after a single vaccination, they induced protective immune response against subsequent CHIKV challenge, characterized by high titers of neutralizing antibodies. The rational design of alphavirus genomes provides a strong basis for the development of new recombinant alphaviruses with irreversible, highly attenuated, cell type-restricted phenotypes.
American Society for Microbiology