Passive Transfer of Immune Sera Induced by a Zika Virus-Like Particle Vaccine Protects AG129 Mice Against Lethal Zika Virus Challenge

Highlights

• Zika virus VLP comprised of structural proteins prME induces high-titer neutralizing antibodies in C57Bl/6 x Balb/c mice.

• Zika virus VLP vaccine-induced antibodies passively transferred to AG129 mice protects against lethal Zika virus challenge.

• Level of circulating neutralizing antibody is correlated with protection against Zika virus challenge.

Zika virus, transmitted by mosquito to humans, poses a serious health threat due to its association with birth defects in developing fetuses and neurological disorders in adults. We sought to develop a Zika vaccine based on virus-like particles (VLPs), which are structurally the same as the parent virus but don't contain genetic material. The Zika VLP vaccine, when administered to mice, induced antibodies. These antibodies, when transferred to a mouse susceptible to Zika virus infection, protected the animals against Zika virus challenge and death. Our results will support continued development of the Zika VLP vaccine and testing in human subjects.

Abstract

Zika virus (ZIKV) poses a serious public health threat due to its association with birth defects in developing fetuses and Guillain-Barré Syndrome in adults. We are developing a ZIKV vaccine based on virus-like particles (VLPs) generated in transiently transfected HEK293 cells. The genetic construct consists of the prM and envelope structural protein genes of ZIKV placed downstream from a heterologous signal sequence. To better understand the humoral responses and correlates of protection (CoP) induced by the VLP vaccine, we evaluated VLP immunogenicity with and without alum in immune-competent mice (C57Bl/6 x Balb/c) and observed efficient induction of neutralizing antibody as well as a dose-sparing effect of alum. To assess the efficacy of the immune sera, we performed passive transfer experiments in AG129 mice. Mice that received the immune sera prior to ZIKV infection demonstrated significantly reduced viral replication as measured by viral RNA levels in the blood and remained healthy, whereas control mice succumbed to infection. The results underscore the protective effect of the antibody responses elicited by this ZIKV VLP vaccine candidate. These studies will help define optimal vaccine formulations, contribute to translational efforts in developing a vaccine for clinical development, and assist in the definition of immunologic CoP.