Purified Inactivated Zika Vaccine Candidates Afford Protection against Lethal Challenge in Mice

Whitney R Baldwin,Elizabeth A Dietrich,Yee Tsuey Ong,Stephanie Sonnberg,Holli A Giebler,Claire Y.-H Huang,Hoang K Danh,Hansi J Dean,Jill A Livengood,Janae L Stovall,Kelly J Bohning,Hetal K Patel,Karen L Boroughs

doi:10.1038/s41598-018-34735-7

Whitney R Baldwin, Elizabeth A Dietrich + Show 11 more

Open Access

https://doi.org/10.1038/s41598-018-34735-7

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Abstract

In response to the 2016 global public health emergency of international concern announced by the World Health Organization surrounding Zika virus (ZIKV) outbreaks, we developed a purified inactivated Zika virus vaccine (PIZV) candidate from ZIKV strain PRVABC59, isolated during the outbreak in 2015. The virus isolate was plaque purified, creating six sub-isolated virus stocks, two of which were selected to generate PIZV candidates for preclinical immunogenicity and efficacy evaluation in mice. The alum-adjuvanted PIZV candidates were highly immunogenic in both CD-1 and AG129 mice after a 2-dose immunization. Further, AG129 mice receiving 2 doses of PIZV formulated with alum were fully protected against lethal ZIKV challenge and mouse immune sera elicited by the PIZV candidates were capable of neutralizing ZIKVs of both African and Asian genetic lineages in vitro. Additionally, passive immunization of naïve mice with ZIKV-immune serum showed strong positive correlation between neutralizing ZIKV antibody (NAb) titers and protection against lethal challenge. This study supported advancement of the PIZV candidate toward clinical development.

Highlights

Zika virus (ZIKV) is a member of Flaviviridae, which includes other human pathogenic flaviviruses such as West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV), dengue virus (DENV) and tick-borne encephalitis virus (TBEV)
Development based on the criteria that it was isolated from a serum sample from a hospitalized patient who was infected in Puerto Rico in late 2015 during the most recent ZIKV outbreak in the Americas, and the isolation history of the virus is well documented
We first amplified the virus in Vero cells in serum-free medium to make our passage 1 stock (P1), and conducted three rounds of virus plaque purification (P2-4) to obtain 6 sub-isolates (a-f)

Summary

Introduction

Zika virus (ZIKV) is a member of Flaviviridae, which includes other human pathogenic flaviviruses such as West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV), dengue virus (DENV) and tick-borne encephalitis virus (TBEV). ZIKV has been linked to severe fetal abnormalities and neurological diseases in both newborns and adults during the recent epidemic in the Americas[10,11,12,13] and retrospectively in French Polynesia[14,15,16]. This global spread of ZIKV in previously naïve populations is reminiscent of other emerging arboviral infectious diseases, such as chikungunya. Purified inactivated vaccines have been developed and safely utilized for the prevention of diseases caused by other flaviviruses, including JEV and TBEV20. Virus stock generation Virus isolate amplified in Vero (2×) and C6/36 (1×) (V2/C6-1) Virus amplification in Vero Plaque purification of P1 Plaque purification of P2 Plaque purification of P3 Amplification of P4 plaques (a-f sub-isolates) in Vero

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