An experimental Zika vaccine reduced the amount of virus in pregnant rhesus macaques and improved fetal outcomes, a new study shows.
The work could help support development and approval of the experimental Zika DNA vaccine VRC5283, which is currently in early stage trials in humans.
The study in Science Translational Medicine marks the first test of a Zika vaccine given before conception with exposure to the virus during pregnancy, says Koen Van Rompay, virologist at the California National Primate Research Center at the University of California, Davis.
Zika virus infection of pregnant women links to a high risk of adverse fetal effects, including fetal death, microcephaly, and other abnormalities, collectively termed congenital Zika syndrome. No approved vaccine is available yet.
Pregnant monkeys get Zika vaccine
Researchers designed the study to mimic a real-world scenario where women could receive vaccination months or years before becoming pregnant.
After vaccinating female monkeys with VRC5283, depending on their reproductive cycles, researchers housed the female animals with males and allowed them to procreate. Thirteen vaccinated animals and 12 unvaccinated controls became pregnant.
The investigators exposed the pregnant animals to Zika virus at intervals representing the first and second trimesters.
Vaccinated females had less virus in their blood, and the virus persisted for a shorter duration after exposure. Two unvaccinated animals lost the fetus early in pregnancy due to Zika virus infection; there was no early fetus loss in the vaccinated group.
At the end of pregnancy, the researchers looked for Zika virus in tissues from the mothers and fetuses. Eleven of 12 fetuses in the unvaccinated control group had detectable Zika virus RNA.
The researchers detected no Zika virus RNA in the 13 fetuses from the vaccinated group, suggesting that the vaccine prevented transmission of virus to the fetus. Antibodies against Zika virus in the vaccinated mother animals correlated with protection against the virus.
Subtle development deficits
The results suggest that VRC5283 vaccine may prevent mother-to-fetus transmission of Zika virus in humans as well, Van Rompay says. The candidate vaccine is currently in global phase IIb trials conducted by the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases to test its safety and ability to elicit an immune response in humans.
Researchers would need to do additional clinical trials to determine efficacy to support licensure of the vaccine. Results from the animal studies will help support the case for approving the vaccine.
Ongoing work with this animal model of Zika virus infection includes evaluation of the ability of passive antibody to the virus to protect against Zika virus infection in pregnancy. Because it takes some weeks for antibodies to develop after a vaccination, passive antibody transfer might be used to immediately treat a pregnant woman who is at risk of getting infected or has symptoms of Zika virus infection.
The researchers are also looking at how Zika virus affects the development of young macaques. Rhesus macaques do not develop the same head malformation (microcephaly) seen in some human infants, Van Rompay says, but this may be a relatively rare complication. Experts think there could be many more infants exposed to Zika virus before birth who may show more subtle developmental deficits.
“In our previous studies, we found microscopic brain lesions in fetuses exposed to Zika virus,” Van Rompay says. The researchers hope that careful monitoring of macaques exposed to the virus before birth for a long time after birth, will point to other problems that might also show up in children.
Additional coauthors are from Duke; University of California, Los Angeles; and UC Davis. The National Institutes of Health and the NIAID Intramural Research Program funded the work.
Source: UC Davis