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Background: We report 2-year persistence of immune response to Takeda's prophylactic purified formalin-inactivated whole Zika virus vaccine candidate (TAK-426) compared with that observed after natural infection., Methods: A randomized, observer-blind, placebo-controlled, dose-selection, phase 1 trial was conducted in 18-49-year-old adults at 9 centers (7 in the United States, 2 in Puerto Rico) from 13 November 2017 to 24 November 2020. Primary objectives were safety, tolerability, and immunogenicity of 3 increasing doses of TAK-426 administered as 2 doses 28 days apart to flavivirus (FV)-naive and FV-primed adults. Here, we report on safety and persistence of immunity up to 2 years after primary vaccination with 10-μg TAK-426, the highest dose, and compare neutralizing antibody responses with those observed after natural infection., Results: TAK-426 at 10-μg had an acceptable safety profile in FV-naive and FV-primed adults up to 24 months after dose 2. Seropositivity for neutralizing antibodies was 100% at 1 year, and 93.8% and 76.2% at 2 years in FV-naive and FV-primed groups, respectively. TAK-426 responses were comparable in magnitude and kinetics with those elicited by natural Zika virus infection., Conclusions: These results support the further clinical development of TAK-426 for both FV-naive and FV-primed populations., Clinical Trials Registration: NCT03343626., Competing Interests: Potential conflicts of interest. C. J. A., F. N., K. J. M., K. B., P. K., M. L., E. W., T. D. P., W. R. B., J. S., and G. D. are employees of Takeda and hold stock/stock options in Takeda. H. H. H., H. P., F. P., and V. M. were employees of Takeda when the study was conducted and may hold stock/stock options in Takeda. E. J. A. reports consultancy for Janssen, Medscape, Pfizer, Sanofi Pasteur, GlaxoSmithKline, and Moderna; safety monitoring boards for Kentucky BioProcessing, Sanofi Pasteur, and WCG and ACI Clinical; institutional clinical research funding from GlaxoSmithKline, Janssen, MedImmune, Merck Sharp & Dohme, Micron, PaxVax, Pfizer, Regeneron, and Sanofi Pasteur; and institutional funding from the National Institutes of Health for clinical research on Moderna and Janssen vaccines. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

In response to the 2016 global public health emergency of international concern announced by the World Health Organization surrounding Zika virus (ZIKV) outbreaks, we developed a purified inactivated Zika virus vaccine (PIZV) candidate from ZIKV strain PRVABC59, isolated during the outbreak in 2015. The virus isolate was plaque purified, creating six sub-isolated virus stocks, two of which were selected to generate PIZV candidates for preclinical immunogenicity and efficacy evaluation in mice. The alum-adjuvanted PIZV candidates were highly immunogenic in both CD-1 and AG129 mice after a 2-dose immunization. Further, AG129 mice receiving 2 doses of PIZV formulated with alum were fully protected against lethal ZIKV challenge and mouse immune sera elicited by the PIZV candidates were capable of neutralizing ZIKVs of both African and Asian genetic lineages in vitro. Additionally, passive immunization of naïve mice with ZIKV-immune serum showed strong positive correlation between neutralizing ZIKV antibody (NAb) titers and protection against lethal challenge. This study supported advancement of the PIZV candidate toward clinical development.