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.

Details

Title
Purified Inactivated Zika Vaccine Candidates Afford Protection against Lethal Challenge in Mice
Author
Baldwin, Whitney R 1 ; Livengood, Jill A 2 ; Giebler, Holli A 1 ; Stovall, Janae L 3 ; Boroughs, Karen L 3 ; Sonnberg, Stephanie 2 ; Bohning, Kelly J 2 ; Dietrich, Elizabeth A 3 ; Ong, Yee Tsuey 3 ; Danh, Hoang K 2 ; Patel, Hetal K 2 ; Huang, Claire Y-H 3   VIAFID ORCID Logo  ; Dean, Hansi J 2 

1  Takeda Vaccines Inc, Cambridge, MA, USA; Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA 
2  Takeda Vaccines Inc, Cambridge, MA, USA 
3  Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA 
Pages
1-13
Publication year
2018
Publication date
Nov 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-34735-7
ProQuest document ID
2130793295
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.