Zika virus like particles elicit protective antibodies in mice

Abstract

Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever. Since its recent emergence in 2014 in the American continent, ZIKV infection during pregnancy has been closely associated with a wide range of congenital abnormalities. To date, no vaccines or antivirals are publicly available. We developed Zika virus-like particles (VLPs) and evaluated their immunogenicity and protective efficacy in mouse models. ZIKV VLPs (ZIKVLPs) formulated with alum were injected into 6-8-week-old interferon deficient AG129 mice as well as wild type BALB/c mice. Control mice received PBS/alum. Animals were challenged with 200 PFU (>1000 AG129 LD50s) of ZIKV strain H/PF/2013. All vaccinated mice survived with no morbidity or weight loss while control animals either died at 9 days post challenge (AG129) or had increased viremia (BALB/c). Neutralizing antibodies were observed in all ZIKVLP vaccinated mice. The role of neutralizing antibodies in protecting mice was demonstrated by passive transfer. Our findings demonstrate the protective efficacy of the ZIKVLP vaccine and highlight the important role that neutralizing antibodies play in protection against ZIKV infection.

Author summary

Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever. During the recent outbreak in South America, ZIKV infection during pregnancy was associated with severe congenital abnormalities. We developed a vaccine against ZIKV utilizing virus-like particles (VLPs). VLPs are structurally similar to viruses, but are not infectious. We injected mutant mice capable of succumbing to ZIKV infection with these VLPs. Mice vaccinated with VLPs survived infection, while negative control mice died. These studies are important because ZIKVLP based vaccines could be tested in humans as a prophylactic candidate with minimal safety concerns able to protect unborn babies whose mothers become infected with Zika virus during pregnancy.