Zika Vaccines

Zika Virus Vaccine Candidates June 2025

Developing a safe and efficacious Zika vaccine and monoclonal antibody (mAb) is a global health priority, says the World Health Organization (WHO). However, as of May 1, 2025, the U.S. Food and Drug Administration (FDA), Brazil, the European Medicines Agency (EMA), and the United Kingdom have not approved any Zika vaccine or monoclonal antibody (mAb). As of June 2025, a review identified 16 Zika vaccine candidates in phase 1 or 2 trials and three mAbs in phase 1 trials. Zika vaccine clinical trials involving a DNA, modified vaccinia Ankara vector platform, and purified inactivated vaccine candidates (January 2023, May 2023, October 2023) demonstrate that vaccine candidates can induce Zika-neutralizing monoclonal antibodies (mAbs). A series of papers published on February 28, 2025, summarizes the crucial challenges and knowledge gaps that need to be addressed to advance Zika vaccine research.

Since 2016, approximately $350 million in research funding for a Zika vaccine has been mobilized (Chapman et al., 2020; U.K.'s Newton Fund, U.S. HHS). The U.S. National Institute of Allergy and Infectious Diseases (NIAID) is developing multiple vaccine candidates to prevent Zika infection.

Valneva's VLA1601 is the most advanced Zika vaccine candidate. It is a second-generation, highly purified, inactivated, adjuvanted vaccine candidate adsorbed on aluminum hydroxide. On March 26, 2024, Valneva Austria GmbH announced the initiation of an additional Phase 1 clinical trial (VLA1601-102), with results expected in the first half of 2025.

ZPIV is a Zika virus vaccine candidate with a purified, formalin-inactivated Zika virus. In June 2023, a study found ZPIV to be well-tolerated in flavivirus-naive and previously vaccinated adults; the immunogenicity of ZPIV in bats varied significantly according to their antecedent flavivirus vaccination status. Immune bias towards the flavivirus antigen of initial exposure and the timing of vaccination may have impacted responses. In this Phase 1 clinical trial, a third ZPIV dose significantly reduced, but did not eliminate, the discrepancy in immunogenicity.

TAK-426 (PIZV) is a purified, inactivated, alum-adjuvanted, whole Zika virus vaccine candidate. It is being tested to provide safety and immunogenicity data for further clinical development.

Brazil-based Butantan Institute is developing a vaccine against the Zika virus. Animal tests are expected to begin in the second half of 2024.

iosBio OraPro-Zika is an orally administered Zika virus vaccine candidate based on a non-replicating human adenovirus type 5 (AdHu5) (E1/E3 deleted) expressing Zika transgenes.

GEO-ZM02 is constructed using a modified vaccinia Ankara vector platform. Preclinical studies demonstrated that a single dose of GEO-ZM02 provided 100% protection against the lethal Zika virus. This Zika vaccine is based on the virus's NS1 protein, which is not associated with the antibody-dependent enhancement of infection.

Ad26.ZIKV.001 is a replication-incompetent human adenovirus serotype 26 (ad26) vector vaccine candidate. In a clinical trial, researchers found that two doses of Ad26 were effective. ZIKV. 001 were safe, causing mild to moderate reactogenicity and inducing persistent neutralizing antibody responses. The single dose had lower peak antibodies but was durable after one year. 

GeneOne Life Science and Inovio Pharmaceuticals' phase 1, open-label clinical trial of the DNA vaccine GLS-5700 elicited anti-ZIKV immune responses. 

VRC5283 is a Zika virus DNA vaccine candidate composed of a single closed-circular DNA plasmid encoded with wild-type precursor transmembrane M and envelope proteins from the H/PF/2013 strain of ZIKV. It is being tested in a phase 2 clinical study.

The University of Adelaide was awarded $1.35 million in funding to develop a novel DNA vaccine, pVAX-tpaNS1, for the treatment of the Zika virus. Dry-coating of pVAX-tpaNS1 on the HD-MAP device resulted in no loss of vaccine stability at 40°C storage over 28 days.

rZIKV/D4Δ30-713 is a live attenuated chimeric Zika candidate vaccine expressing the premembrane (prM) and envelope (E) genes of a contemporary ZIKV strain within a dengue DEN4Δ30 background. It completed a phase 1 clinical trial. The researchers wrote: Our results suggest rZIKV/DEN4Δ30 is over-attenuated and thus will not be further developed as a candidate ZIKV vaccine.

ZikaEnv:aghFc is a plant-based recombinant vaccine that transiently expresses the ZIKV envelope protein. At a low dose (1–5 μg), it induces humoral and cellular immunity.

Duke-NUS researchers used live-attenuated vaccine (ZIKV-LAV) strains of the Zika virus, which are weakened viruses with a limited ability to infect healthy cells.

ZIKV E DIII-specific antibody ZK2B10, isolated from a ZIKV convalescent individual, is being developed by Uvax Bio.

Research suggests that the novel, auto-adjuvanted, virus-like particles technology EDIII-QβVLP vaccine is a promising candidate for preventing ZIKV infection, with potential applications in combating this and other emerging flaviviruses.

Zika and Dengue Infections

A significant safety concern for vaccine development against ZIKV is the antibody-dependent enhancement of infection between ZIKV and the Dengue virus. Preexisting immunity to ZIKV has been recognized as a factor that can aggravate subsequent Dengue infection in animal models and humans.

Zika Outbreaks

Zika outbreaks have been confirmed in numerous countries in April 2025.

Zika Vaccine News

January 20, 2025 - The Liverpool School of Tropical Medicine reported that the Zika virus hijacks the skin of its human host to send out chemical signals that lure more mosquitoes to infect and spread the disease further, according to new research.

March 26, 2024 - Valneva Initiates Phase 1 Trial of Second-Generation Zika Vaccine Candidate.

January 8, 2024 - A review of the Zika vaccine development.

December 27, 2023 - A study showed that our plant-based recombinant subunit ZIKV vaccine afforded substantial protective immunity. This immunity was vertically transferred, protecting the next generation of mice against ZIKV infection.

December 2, 2023 - A needle-free vaccine patch is being developed to protect people from the Zika virus. A prototype high-density microarray patch shows promise in preclinical studies for delivering a novel, needle-free vaccine against the Zika virus.

June 27, 2023 - The Lancet Infectious Diseases published a phase 1 study that found ZPIV was well tolerated in flavivirus-naive and primed adults, and humoral immune responses rose substantially following a third dose of ZPIV.

April 19, 2023 - Article: Scientists find different flavors of broadly neutralizing antibodies that could lead to new vaccines for growing threats.

April 1, 2023 - The journal Nature published results from a study: An effective live-attenuated Zika vaccine candidate with a modified five ′ untranslated region. These results suggest that modifying the ZIKV 5′ UTR is a novel strategy to develop live-attenuated vaccine candidates for ZIKV and potentially for other flaviviruses.

January 25, 2023 - GeoVax Labs, Inc. confirmed that the U.S. Patent and Trademark Office issued a Notice of Allowance for Patent Application No. 17/000,768 titled "Method for Generating a ZIKV Immune Response Utilizing a Recombinant Modified Vaccinia Ankara Vector Encoding the NS1 Protein."

January 19, 2023: The Lancet Infectious Diseases published a study titled "The safety and immunogenicity of two Zika virus mRNA vaccine candidates in healthy flavivirus baseline seropositive and seronegative adults: the results of two randomized, placebo-controlled, dose-ranging, phase 1 clinical trials." These findings support the continued development of mRNA-1893 against the ZIKV.

May 18, 2021 - The Lancet published a study that concluded that TAK-426 was well-tolerated, had an acceptable safety profile, and was immunogenic in both flavivirus-naive and flavivirus-primed adults. Based on the safety and immunogenicity profiles of all TAK-426 doses assessed, the 10 μg TAK-426 amount was selected for further clinical development.

February 16, 2021 - The Zika virus candidate, Ad26.ZIKV.001, a replication-incompetent human adenovirus serotype 26 (Ad26) vector, demonstrated promising safety and immunogenicity in Phase I clinical trials. Researchers say the vaccine warrants further development should the need reemerge.

August 7, 2020 - A study describes the preclinical selection and development of a potent ZIKV vaccine from 9 constructs using SAM technology, which expresses various forms of the ZIKV prM-E antigen. This study identified one ZIKV SAM vaccine candidate, VRC5283, and demonstrated that two wholly protected mice and nonhuman primates were resistant to the ZIKV challenge.

April 15, 2020 - Moderna's Zika vaccine, mRNA1893, at low-dose levels, was highly effective.

December 19, 2019 - A U.S. NIH-developed Zika vaccine improves fetal outcomes in an animal model.

November 28, 2017 - Takeda Pharmaceutical announced that its purified, inactivated, alum-adjuvanted whole Zika virus vaccine candidate, TAK-426, has progressed into a Phase 1 clinical trial.