Protective efficacy of Zika vaccine in AG129 mouse model

K Sumathy,Usha Praturi,Krishna M Ella,Sampath Kumar Ponnuru,Ravi Kumar Gondu,Sindhuja Gadiyaram,Nagaraju Bonguram,Bhushan Chougule,Bharathi Kulkarni,Latha Karunakaran,Rakesh Eligeti

doi:10.1038/srep46375

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes asymptomatic infection or presents only mild symptoms in majority of those infected. However, vaccination for ZIKV is a public health priority due to serious congenital and neuropathological abnormalities observed as a sequelae of the virus infection in the recent epidemics. We have developed an inactivated virus vaccine with the African MR 766 strain. Here we show that two doses of the vaccine provided 100% efficacy against mortality and disease following challenge with homotypic MR 766 and the heterotypic FSS 13025 ZIKV strains in the Type I and Type II interferon deficient AG129 mice. Two doses of the vaccine elicited high titer of neutralizing antibodies in Balb/c mice, and the vaccine antisera conferred protection against virus challenge in passively immunized mice. The studies were useful to rationalize vaccine doses for protective efficacy. Furthermore, the vaccine antisera neutralized the homotypic and heterotypic ZIKV strains in vitro with equivalent efficiency. Our study suggests a single ZIKV serotype, and that the development of an effective vaccine may not be limited by the choice of virus strain.

Highlights

Cambodia[24] and belongs to the Asian genotype
Death in the control groups challenged with MR 766 occurred earlier with mean time to death (MTD) of 8 days as compared to the group challenged with FSS 13025 with MTD of 12 days (Fig. 1a)
The envelope E protein is the target of Zika virus (ZIKV) neutralizing antibodies[25,26]

Summary

Introduction

Cambodia[24] and belongs to the Asian genotype. Protective efficacy in AG129 mice complemented the robust immune response elicited by the vaccine in Balb/c mice. To study the immune responses induced by the alum adsorbed purified inactivated ZIKV vaccine, we immunized Balb/c mice (n = 8/group) with two doses of 5 μg or 10 μg of the vaccine, and the control group with alum (placebo) by intramuscular route on day 0 and on day 21 as schematically outlined in Supplementary Fig. S1a,b. Protective efficacy of the vaccine was assessed in the vaccinated and in control groups by intravenous injection of 105 PFU of MR 766 and the virus titers in plasma were estimated every 24 hours up to 144 hours post-infection.

Results

Conclusion