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Sci Transl Med. 2019 May 15;11(492). pii: eaav3113. doi: 10.1126/scitranslmed.aav3113.

A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates.

Author information

1
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2
Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
3
Pathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
4
Biosecurity Research Institute and Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
5
Center for Aerobiological Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
6
Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA.
7
Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA.
8
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jmascola@mail.nih.gov gary.nabel@sanofi.com srinivas.rao@sanofi.com.

Abstract

Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV, respectively) are important mosquito-borne agents that pose public health and bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there are currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated a trivalent, or three-component, EEV vaccine composed of virus-like particles (VLPs). Monovalent VLPs elicited neutralizing antibody responses and protected mice and nonhuman primates (NHPs) against homologous challenges, but they were not cross-protective. In contrast, NHPs immunized with trivalent VLPs were completely protected against aerosol challenge by each of these three EEVs. Passive transfer of IgG from immunized NHPs protected mice against aerosolized EEV challenge, demonstrating that the mechanism of protection was humoral. Because they are replication incompetent, these trivalent VLPs represent a potentially safe and effective vaccine that can protect against diverse encephalitis viruses.

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