Frolov I. 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 struc-tural 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. Alphaviruses are a group of widely distributed human and animal pathogens (17). Most of them are transmitted by mos-quito vectors among vertebrate hosts, in which they cause diseases of various severities (21). Some of the alphaviruses, such as Venezuelan equine encephalitis virus (VEEV), East-ern equine encephalitis virus (EEEV), and Western equine encephalitis virus, are known to induce encephalitis in humans