Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus

Background Zika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barre syndrome in adults. To date, there are no approved vaccines against ZIKV infection. Various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for ZIKV. Methodology/Principle findings We have developed a ZIKV vaccine candidate based on Virus-Like-Particles (VLPs) produced in HEK293 mammalian cells using the prM (a precursor to M protein) and envelope (E) structural protein genes from ZIKV. Transient transfection of cells via plasmid and electroporation produced VLPs which were subsequently purified by column chromatography yielding approximately 2mg/L. Initially, immunogenicity and efficacy were evaluated in AG129 mice using a dose titration of VLP with and without Alhydrogel 2% (alum) adjuvant. We found that VLP with and without alum elicited ZIKV-specific serum neutralizing antibodies (nAbs) and that titers correlated with protection. A follow-up immunogenicity and efficacy study in rhesus macaques was performed using VLP formulated with alum. Multiple neutralization assay methods were performed on immune sera including a plaque reduction neutralization test, a microneutralization assay, and a Zika virus Renilla luciferase neutralization assay. All of these assays indicate that following immunization, VLP induces high titer nAbs which correlate with protection against ZIKV challenge. Conclusions/Significance These studies confirm that ZIKV VLPs could be efficiently generated and purified. Upon VLP immunization, in both mice and NHPs, nAb was induced that correlate with protection against ZIKV challenge. These studies support translational efforts in developing a ZIKV VLP vaccine for evaluation in human clinical trials. Author summary Zika virus (ZIKV) is a significant global health threat particularly due to the speed in which epidemics can occur. The resulting infections have been demonstrated to harm a developing fetus and, in some adults, be a co-factor for the development of Guillain-Barre syndrome. ZIKV is typically spread by the Aedes mosquito, but sexual transmission is also possible. We sought to develop a ZIKV prophylactic vaccine based on surface glycoproteins of the virus that would be devoid of any viral genetic material. This Virus-Like-Particle (VLP) was generated in vitro following introduction of plasmid DNA encoding Zika structural protein (prM-E) genes into mammalian cells. The aluminum-adjuvanted VLP induced nAbs in mice and nonhuman primates and protected against ZIKV challenge in vivo. These studies support the evaluation of this VLP candidate vaccine in human clinical trials.

Automated summary

A Zika virus-like particle (VLP) vaccine was developed using genetically engineered VLPs, which induced protective neutralizing antibodies in both mice and nonhuman primates, supporting further evaluation in human clinical trials.