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

• Published in: Scientific reports Vol. 8; no. 1; pp. 16509 - 13
• Main Authors: Baldwin, Whitney R., Livengood, Jill A., Giebler, Holli A., Stovall, Janae L., Boroughs, Karen L., Sonnberg, Stephanie, Bohning, Kelly J., Dietrich, Elizabeth A., Ong, Yee Tsuey, Danh, Hoang K., Patel, Hetal K., Huang, Claire Y.-H., Dean, Hansi J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.11.2018; Nature Publishing Group
• Subjects: 101/28; 13/106; 38/1; 38/90; 45/23; 45/29; 631/250/590/1883; 631/326/590/1883; 64/60; 82/16; Aluminum sulfate; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Candidates; Cell Line; Chlorocebus aethiops; Disease Models, Animal; Humanities and Social Sciences; Immune serum; Immune system; Immunization; Immunization (passive); Immunization, Secondary; Immunogenicity; Immunogenicity, Vaccine - immunology; Mice; multidisciplinary; Outbreaks; Public health; Science; Science (multidisciplinary); Vaccines; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - immunology; Vero Cells; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - immunology; Zika virus; Zika Virus - genetics; Zika Virus - immunology; Zika Virus - ultrastructure; Zika Virus Infection - immunology; Zika Virus Infection - prevention & control; Zika Virus Infection - virology; ZIKV Strain; ZIKV Challenge; Aged Mice; Zika Virus (ZIKV); ZIKV Vaccine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-34735-7

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.