Rapid travel to a Zika vaccine: are we heading towards success or more questions?

ABSTRACT

Introduction: The emergence of the Zika virus (ZIKV) in Latin America in 2015–2016 led to an expeditious search for vaccine candidates, with a DNA-based candidate having progressed to Phase II. However, several features of ZIKV infection and epidemiology are not understood, which may be key to maximizing efficacy and ensuring safety of ZIKV vaccines.

Areas covered: Conceivable problems related to vaccine development and policy include: (1) paucity of diagnostics to satisfactorily discriminate between past ZIKV and dengue virus (DENV) exposure; (2) insufficient knowledge of the mechanisms of ZIKV neurovirulence, amongst other unknowns in the biology of this infection, is particularly relevant from a vaccine safety perspective; and (3) the potential for disease enhancement, as observed with DENV infection and vaccine.

Expert opinion: Vaccine candidates that entered phase I/II trials have demonstrated protection in naïve animal models, while ZIKV epidemics occurred in populations that had encountered DENV before. The resulting cross-reactive antibodies pose problems for reliable serologic diagnostic assays, and for the potential of disease enhancement. The alleged neurological complications also warrant further exploration in order to reassure regulators of the safety profile of these vaccines in target populations. These research aspects should be an integral part of the efforts to develop a vaccine.

KEYWORDS:

• Antibody dependent enhancement
• diagnostic
• neurological complications
• serology
• vaccines
• zika virus

Article highlights

• The development of vaccine candidates against ZIKV infections is hampered by the lack of specific serological diagnostic assay, the unknowns relating to the neurological complications and the possibility of antibody-dependent enhancement.

• Accurate evaluation of vaccine efficacy may only be possible after licensure, if only immunological endpoints and safety data are used for clinical development.

• The cross-reactive antibodies between DENV and ZIKV infection complicates approaches to vaccine development and implementation, if an antibody-dependent enhancement phenomenon is confirmed for ZIKV infection and vaccine-inducing antibodies.

• The identification of a correlate/surrogate of protection is required.

• The scientific community must reach a consensus on the neurological complications associated with ZIKV infection, and prove beyond reasonable doubt that the ZIKV vaccine candidates do not increase the risk of these complications.

This box summarizes key points contained in the article.

Declaration of interest

A Reyes-Sandoval is an inventor on a patent filed for a ZIKV vaccine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

C Rollier is supported by the National Institute for Health Research Oxford Biomedical Research Centre. A Reyes-Sandoval and C Rollier are Jenner Institute investigators.