title: A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection.
abstract: Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Wataru
authors.initials: W
authors.lastname: Akahata
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Hanne
authors.initials: H
authors.lastname: Andersen
authors.forename: Siyang
authors.initials: S
authors.lastname: Sun
authors.forename: Heather A
authors.initials: HA
authors.lastname: Holdaway
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Stephen
authors.initials: S
authors.lastname: Higgs
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rao
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D002478:Cells, Cultured; D002646:Chikungunya virus / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; D014765:Viral Vaccines