Zika Virus Neutralizing Antibody Responses Elicited by Vaccination or Infection

Background Zika virus (ZIKV) emergence in 2015–2016 was characterized by high attack rates and a wave of Congenital Zika Syndrome cases that affected several countries in the Americas. The sudden drop in virus transmission in the following years and the lack of a reliable correlate of protection have hampered the development of vaccines. ZIKV neutralizing antibodies (nAbs) responses to natural ZIKV infection provide insights into the potential efficacy of vaccine candidates. Methods In this study, we compared anti-ZIKV nAb responses generated by a ZIKV vaccine (TAK-426), to those elicited by natural ZIKV infection in participants from diverse geographic areas using the same neutralizing antibody assay. Results Those with a ZIKV infection (inapparent or symptomatic) exhibited higher levels of ZIKV nAbs, than TAK-426 vaccine recipients at all time points. The differences were less pronounced 1 month after TAK-426 dose 2. ZIKV nAb titers in vaccinated recipients were above the calculated threshold of protection at 1 month post-dose 2 for flavivirus (FV)-naive participants and at 1 and 6 months post-dose 2 for FV-primed participants. The kinetics of ZIKV nAbs were similar for both the natural infection and vaccination groups, exhibiting a peak, decline, and stabilization pattern; however, vaccine non-inferiority was not demonstrated. Conclusions Our findings suggest that nAbs evoked by the current phase 1 formulation and dosage of TAK-426 may not protect against a ZIKV infection in endemic countries and that a booster dose should be further evaluated.