Inactivated Zika virus vaccine does well in phase 1 trials

Scientists at the Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, are developing a vaccine for Zika, and have shown, in initial results from three phase 1 clinical trials, that an investigational Zika purified inactivated virus (ZPIV) vaccine is well tolerated and elicited an immune response. Their results are published in The Lancet.

“A vaccine is urgently needed to help prevent Zika infection, which can cause birth defects and other developmental abnormalities in babies born to infected women, as well as a constellation of other health problems in infected adults and children,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID). “We are encouraged by initial clinical trial results that indicate the ZPIV vaccine is safe and immunogenic, data that support additional clinical testing of the vaccine to determine its ability to prevent Zika virus infection.”

Initial studies were randomized, double-blind, placebo-controlled phase 1 trials in 67 adults. Fifty-five received the ZPIV vaccine, comprised of two doses administered intramuscularly 4 weeks apart with an adjuvant to induce a stronger immune response, and 12 received a placebo.

A full 92% of ZKIV recipients had seroconverted (microneutralization titers ≥ 1:10) by day 57. Peak geometric mean titers were seen at day 43 and were greater than protective thresholds seen in preclinical studies.

The antibodies were transferred to mice, which were then infected with the actual Zika virus. Researchers found that the transferred antibodies conferred robust protection against Zika viremia in the mice. Further testing is under way to determine the precise antibody concentrations needed to protect against congenital infection.

Adverse events experienced by the ZKIV recipients included injection-site pain (60%) or tenderness (47%), fatigue (43%), headache (39%), and malaise (22%).

“Zika remains a threat to US military personnel and families of service members. We aim to develop a vaccine to protect the military, as well as the global community," said Col. Nelson Michael, Zika program leader at the WRAIR.

Additional research on ZPIV will assess dosing, schedule, and prior immunity. Researchers at WRAIR are also evaluating the impact of preexisting immunity through vaccination with yellow fever or Japanese encephalitis vaccines before commencing with a ZPIV vaccine regimen. These two viruses are members, like Zika, of the Flavivirus family.

Several additional studies of Zika are also concurrently under way. Researchers at Ponce Health Sciences University, Puerto Rico, also plan to study subjects previously exposed naturally to a Flavivirus, like dengue. At Saint Louis University, St. Louis, MO, researchers are attempting to determine the optimal dose of ZPIV by randomizing patients to high, moderate, or low doses. Researchers at Beth Israel Deaconess Medical Center, Boston, MA, are also testing dosing schedules of ZPIV.

Finally, researchers at NIAID, part of the National Institutes of Health, are investigating additional Zika vaccine candidates, including an experimental DNA vaccine currently in phase 2 trials in the US, Central America, and South America. They are also developing an investigational messenger RNA Zika vaccine, as well as a live-attenuated vaccine candidate that will protect against Zika and all four strains of the dengue virus.

These trials are co-funded by the WRAIR and NIAID, part of the National Institutes of Health (NIH).