Research in context
Evidence before this study
The Zika virus outbreak has had devastating effects on children and families across the western hemisphere since 2015. Although no longer declared a public health emergency of international concern, cases of Zika virus infection are still occurring, and the threat of a resurgent epidemic remains. Thus, a safe and effective vaccine is needed to prevent and control Zika virus spread and the consequent complications. The Walter Reed Army Institute of Research, Silver Spring, MD, USA, applied its long-standing expertise, infrastructure, and partnerships in developing and testing vaccines against other flaviviruses to enable rapid design, manufacture, and assessment of an inactivated and purified whole Zika virus vaccine with aluminium hydroxide gel adjuvant. Throughout the development and testing of this vaccine, we searched the biomedical literature for new information on Zika virus and associated countermeasures. We searched PubMed with the terms “Zika”, “flavivirus”, “congenital Zika syndrome”, “vaccine”, “Zika vaccine”, and “flavivirus vaccine” for articles published up to Oct 31, 2017, with no other parameters applied. We additionally reviewed electronic updates from the Centers for Disease Control and Prevention, WHO, and the Pan-American Health Organization on the dynamic epidemiology of the Zika epidemic, and tracked other clinical trials of Zika virus registered with ClinicalTrials.gov. Several Zika vaccine platforms have shown efficacy in preclinical animal studies. One study has reported on the safety and immunogenicity of a DNA vaccine. We found no reports of inactivated Zika virus vaccine being tested in human beings.
Added value of this study
Our purified formalin-inactivated Zika virus vaccine candidate showed a tolerable safety profile and yielded immunogenicity characterised by neutralising antibody titres that exceeded the protective threshold seen in non-human primate studies. Our findings will be useful to the continuing effort to develop a preventive vaccine against Zika virus. Additionally, passive antibody transfer from the serum of vaccine recipients into mice indicated a potential mechanistic correlate of protection.
Implications of all the available evidence
The whole inactivated virus platform on which our Zika vaccine candidate is based has resulted in several safe and effective vaccines, including some licensed for other flaviviruses, such as Japanese encephalitis and tick-borne encephalitis. Our results and previous findings suggest that the inactivated platform is a viable candidate for advanced development.