Abstract
Since its peak in early 2016, the incidence of Zika virus (ZIKV) cases has declined to such low levels that Phase 3 field efficacy trials may be infeasible. While great progress was made to rapidly advance several vaccine candidates into Phase 1 and 2 clinical trials, in the absence of sustained viral transmission it may be difficult to evaluate the effectiveness of ZIKV vaccine candidates by conducting traditional clinical disease endpoint efficacy studies. However, ZIKV is still circulating at low levels in some areas and is likely to re-emerge in naïve populations or in sites of prior epidemics once population immunity wanes. Therefore, the public health need for a ZIKV vaccine remains. To facilitate continued ZIKV vaccine development efforts, the World Health Organization's Initiative for Vaccine Research and the National Institutes of Health’s National Institute of Allergy and Infectious Diseases co-hosted a meeting of experts in March 2018 to identify strategies to demonstrate vaccine effectiveness in view of waning ZIKV disease incidence. This paper outlines points for consideration for developers, regulators, and other stakeholders working towards a licensed ZIKV vaccine. These deliberations may also be applicable to development of vaccines for other emerging infections where the size, unpredictability, and ephemeral nature of outbreaks makes clinical disease endpoint efficacy trials to demonstrate vaccine effectiveness infeasible.
Highlights
The World Health Organization (WHO) declared the cluster of congenital microcephaly cases and other neurological disorders reported in Brazil as a result of Zika virus (ZIKV) infection of pregnant mothers and their infants to be a Public Health Emergency of International Concern (PHEIC) in February 2016
External experts to WHO advised prioritizing the development of a ZIKV vaccine, acknowledging that such development of medical countermeasures remains imperative for a potential further future outbreak [1]
Tremendous progress has been made in ZIKV vaccine development since the WHO declaration of PHEIC in February 2016
Summary
The World Health Organization (WHO) declared the cluster of congenital microcephaly cases and other neurological disorders reported in Brazil as a result of Zika virus (ZIKV) infection of pregnant mothers and their infants to be a Public Health Emergency of International Concern (PHEIC) in February 2016. One or more pivotal Phase 3 trials is normally used to demonstrate safety and efficacy [13]; pre-licensure clinical trials are typically randomized and controlled and are conducted in areas with sufficient disease transmission to estimate vaccine efficacy against a clinical disease endpoint [14]. With low incidence of ZIKV transmission and the unpredictable nature of future outbreaks and consequent difficulty with future field trials, opportunities to conduct randomized-controlled clinical disease endpoint efficacy trials of ZIKV vaccine candidates may be past. This presents challenges for evaluation of efficacy of ZIKV vaccine candidates. This paper outlines points for consideration for developers, regulators, and other stakeholders working towards a licensed ZIKV vaccine (Box 1)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
