title: Chimeric Chikungunya viruses are nonpathogenic in highly sensitive mouse models but efficiently induce a protective immune response.
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.
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Eryu
authors.initials: E
authors.lastname: Wang
authors.forename: Dal Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002646:Chikungunya virus / Q000276:immunology* / Q000472:pathogenicity*; D004195:Disease Models, Animal; D051379:Mice; D012376:Rodent Diseases / Q000276:immunology / Q000821:virology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines