Considerations for the development of Zika virus vaccines.

The current Zika virus outbreak has galvanized the public health community, resulting in calls for rapid action from entities including the World Health Organization and the United States government. The response to Zika virus is perhaps the first of its kind, and it has been influenced by the lessons learned from the response to the 2014 Ebola virus outbreak inWest Africa. However, Zika virus is not Ebola virus. Prior to 2016, there were only 133 publications on ‘‘Zika” in the PubMed database, and a large number of these publications were commentaries or reviews lacking primary research data. In contrast, work had been underway for decades on the development of an Ebola virus vaccine, laying the groundwork for an expedited response in 2014. The broader research community’s extensive experience with dengue virus vaccine development and with the pros and cons of different vaccine platforms has led to speculation that a Zika virus vaccine can be accelerated, potentially with clinical trials initiating by the end of 2016 [1]. However, there are unique attributes of Zika virus, as well as many unanswered questions about the virus, that will need to be considered before a potential vaccine is administered to the public. The close phylogenetic relationship between the flaviviruses has complicated diagnostic efforts for multiple members of this family, because antibody elicited by the viruses is cross-reactive [2]. Definitive diagnosis of Zika virus infection in individuals with previous flavivirus infection therefore requires detection of viral RNA by PCR, which is only achievable during approximately a two week window early in infection. Efforts are underway to develop serological assays to differentiate the flavivirus infections, which would significantly advance our understanding of the epidemiology of Zika virus. However, the cross-reactivity of antibody elicited by other flaviviruses with Zika virus may be more than a diagnostic inconvenience. Cross-reactivity will need to be considered in the context of the efficacy of potential vaccine candidates in the at-risk population. 2. Factors affecting vaccine development