Research ArticleEMERGING INFECTIONS

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

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Science Translational Medicine  15 May 2019:
Vol. 11, Issue 492, eaav3113
DOI: 10.1126/scitranslmed.aav3113

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A triple threat to equine encephalitis viruses

There are no approved treatments or vaccines for certain alphaviruses that can cause fatal encephalitis. Ko et al. designed a trivalent vaccine to simultaneously fend off Eastern, Western, and Venezuelan equine encephalitis viruses. The vaccine is composed of noninfectious virus-like particles and completely protected mice and nonhuman primates from all three viruses. There was no evidence of central nervous system infection or pathology in trivalent virus-like particle–immunized nonhuman primates. Passive transfer experiments revealed that humoral immunity delivered protection from viral challenge. Phase 1 studies are currently being started to test this trivalent vaccine in people.

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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