The research is a collaboration between the Trudeau Institute, the Southwestern National Primate Research Center (SNPRC) of the Texas Biomedical Research Institute, and the Walter Reed Army Institute of Research (WRAIR), where the vaccine was developed.
A vaccine candidate against the Zika virus is effective in preventing its transmission from mother to fetus in preclinical animal studies, according to a new study published in the journal npj Vaccines.
"The vaccine has been shown to be safe for non-pregnant people, but of course we need to know if it is safe and effective for those who are most at risk: pregnant women and their fetuses," says Dr. In-Jeong Kim , a viral immunologist at the Trudeau Institute and first author of the paper. "Our proof-of-concept studies conducted at Trudeau and Texas Biomed show very promising results that the vaccine administered before pregnancy will provide high levels of protection for mothers and babies."
The 2015-2016 Zika outbreak in Brazil and other countries in the Americas led to an increase in spontaneous abortions and a constellation of birth defects, called Zika Congenital Syndrome, including abnormally small heads and neurodevelopmental disorders. This led the World Health Organization to declare the Zika outbreak a public health emergency of international concern.
"It’s important to test vaccines before the next big outbreak, because there will be another one," says Dr. Jean Patterson, a virologist at Texas Biomed and lead author of the paper. "Zika is part of a family of viruses that is known to go through cycles. These viruses tend to spread rapidly through naïve populations that have never been exposed to the virus before, then infections decline for years because most people "They have been exposed. As more and more people are born, there is a new group of naïve individuals for whom the virus can wreak havoc again. We want to help break that cycle."
The WRAIR team developed the purified and inactivated Zika vaccine (ZPIV) using the same technology they used to develop a vaccine against Japanese encephalitis. The vaccine has been tested in non-pregnant animals, showing that it effectively eliminates the virus from the blood. In Phase 1 trials in humans, it has been shown to be safe and elicit a protective immune response.
However, rigorous testing to show that the vaccine protects women and their fetuses from both infection and serious malformations is restricted for safety and ethical reasons. That’s where animal models come into play.
The Trudeau Institute and Texas Biomed evaluated the vaccine in pregnant mice and marmosets, respectively. Studies with mice, led by Kim and Dr. Marcia Blackman, a viral immunologist at Trudeau, showed that the vaccine prevented about 80% of fetal malformations, and that antibodies capable of neutralizing the virus were detected in fetal blood samples eight days old. after infection.
"We were able to detect maternal antibodies in the fetus during pregnancy, and the results suggest that antibodies play a critical role in protecting fetuses against the Zika virus," Kim says.
Marmosets, which are small primates, are more sensitive to Zika infection than other non-human primates; Previous studies showed that fetuses aborted within two weeks of maternal infection.
In the current study, four marmosets were immunized with the ZPIV vaccine. After becoming pregnant, they were exposed to the Zika virus. Only 1 of the 12 offspring tested positive for the Zika virus, demonstrating an effectiveness of more than 90%.
"Because the animals became pregnant at different times, our study was able to show that the vaccine confers protection for at least 18 months after vaccination, which is important to demonstrate long-lasting immunity," says Patterson.
Researchers are already testing what happens when the vaccine is given during pregnancy.
"These studies add evidence that the Zika vaccine developed by WRAIR not only protects animals against Zika virus infection, but also against birth defects that mimic what has been seen in people," says Dr. Kayvon Modjarrad, who directs the U.S. Army’s Zika vaccine program and is director of WRAIR’s emerging infectious diseases branch. "Together with early phase clinical trials, we believe these data provide further support that this vaccine platform is a viable approach to counter the persistent threat of Zika."
Collaborators on npj Vaccines’ work also include: University of Illinois Chicago; University of California, Davis; University of California, San Francisco; and State University of New York, Upstate Medical University.
The research is supported by the Department of Defense and the Office of the Director of the National Institutes of Health, under grant P51OD011133.
