Effects of candidate vaccines against Zika virus infection: A systematic review of the clinical trials

INTRODUCTION: The 2015-2016 Zika virus (ZIKV) pandemic revealed a pathogenic potential, including Guillain-Barré syndrome and Congenital Zika Syndrome (CZS). Despite the decline in incidence, the potential for future circulation and the absence of specific antivirals underscore continued scientific interest in prophylactic vaccine development. OBJECTIVE: To synthesize evidence from clinical trials regarding the safety and preliminary immunogenicity of current ZIKV vaccine candidates. METHODS: This systematic review followed PRISMA guidelines (CRD420251056463). Searches were performed in MEDLINE, Embase, Web of Science, SciELO, and LILACS for clinical trials published between 2015 and 2025. Risk of bias was assessed using the Cochrane RoB 2 tool. RESULTS: Ten Phase 1 clinical trials were included, evaluating four platforms: inactivated virus (ZPIV, TAK-426, VLA1601), DNA (GLS-5700, VRC5283), mRNA (mRNA-1325, mRNA-1893), and viral vector (Ad26.ZIKV.001). All candidates demonstrated acceptable safety profiles, with predominantly mild-to-moderate and transient adverse events (e.g., injection site pain, fatigue, and headache); no vaccine-related serious adverse events were reported. Most platforms induced robust neutralizing antibody responses. Specifically, TAK-426 showed immune persistence for up to two years, while mRNA-1893 maintained responses for 13 months. The viral vector vaccine (Ad26.ZIKV.001) achieved 100% seroconversion with a single dose. Previous orthoflavivirus exposure did not significantly hinder vaccine-induced immunogenicity. Most studies presented a low risk of bias. CONCLUSIONS: ZIKV vaccine candidates across diverse technological platforms are safe and highly immunogenic. The evidence of long-term durability and the success of single-dose or mRNA regimens support the progression of the most promising candidates to Phase 2/3 trials.