Abstract
A critical global health need exists for a Zika vaccine capable of mitigating the effects of future Zika epidemics. In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. Indian rhesus macaques received two doses of PIZV at varying concentrations ranging from 0.016 µg − 10 µg and were subsequently challenged with ZIKV six weeks or one year following the second immunization. PIZV induced a dose-dependent immune response that was boosted by a second immunization. Complete protection against ZIKV infection was achieved with the higher PIZV doses of 0.4 µg, 2 µg, and 10 µg at 6 weeks and with 10 ug PIZV at 1 year following vaccination. Partial protection was achieved with the lower PIZV doses of 0.016 µg and 0.08 µg. Based on these data, a neutralizing antibody response above 3.02 log10 EC50 was determined as a correlate of protection in macaques. PIZV elicited a dose-dependent neutralizing antibody response which is protective for at least 1 year following vaccination.
Highlights
In 2015 and 2016, large outbreaks of Zika virus (ZIKV) occurred in the Americas
We assessed the persistence of immunity and efficacy 1 year following administration of the second purified inactivated Zika vaccine (PIZV) dose, to evaluate neutralizing antibody kinetics and long-term protection
We demonstrated that PIZV elicits a dose-dependent response of both Zika neutralizing and anti-Zika IgG antibodies
Summary
In 2015 and 2016, large outbreaks of Zika virus (ZIKV) occurred in the Americas. These outbreaks were associated with clusters of congenital microencephaly and other severe neurological sequelae in infections in approximately 1 of 7 infants born to pregnant women with laboratory confirmed Zika in the US and US territories[1]. The risk of re-emergence and the severe consequences of infection in pregnant women demonstrate that the need for an effective Zika vaccine remains. The purified inactivated Zika vaccine (PIZV) has previously been evaluated in mouse models and was immunogenic in AG129 and CD1 mice and protected AG129 mice against lethal ZIKV challenge[16]. In those studies, Baldwin et al demonstrated that neutralizing antibodies correlate with protection in AG129 mice. To further evaluate immunogenicity and efficacy of PIZV, we conducted three ZIKV challenge studies in rhesus macaques. We assessed the persistence of immunity and efficacy 1 year following administration of the second PIZV dose, to evaluate neutralizing antibody kinetics and long-term protection
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