@article{d7ab1b157b0846408b64abd0eab35805,
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.",
author = "Wataru Akahata and Yang, {Zhi Yong} and Hanne Andersen and Siyang Sun and Holdaway, {Heather A.} and Kong, {Wing Pui} and Lewis, {Mark G.} and Stephen Higgs and Rossmann, {Michael G.} and Srinivas Rao and Nabel, {Gary J.}",
note = "Funding Information: We thank K. Nagashima for help with electron microscopy and J.D. Yoder for initiating cryoelectron microscopy reconstruction. We also thank A. Tislerics and J. Stein for help with manuscript preparation, B. Hartman for graphic arts and members of the Nabel lab for helpful discussions. We thank R. Seder and D.D. Pinschewer (Department of Pathology and Immunology, University of Geneva) for their kind gift of Ifnar1–/–mice, A. Ault, J.-P. Todd, A. Zajac, C. Chiedi (Vaccine Research Center) and D. Gordon (Bioqual) for plaque assay and processed animal blood samples, J. Greenhouse for RT-PCR assay, B.W. Finneyfrock, T. Jenkins and A. Dodson for animal sampling and care, K. Foulds, M. Donaldson and M. Roederer for monkey sample procedures and J. Lee for preparing 293F cells for VLP production. This research was supported by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health.",
year = "2010",
month = mar,
doi = "10.1038/nm.2105",
language = "English (US)",
volume = "16",
pages = "334--338",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "3",
}