A researcher holds a tray of Zika virus growing in animal cells at Washington University School of Medicine in St. Louis. There is no treatment available to block Zika virus in a pregnant woman from infecting her fetus and potentially causing severe birth defects. But researchers have identified a human antibody that prevents, in pregnant mice, the fetus from becoming infected and the placenta from being damaged. The antibody also protects adult mice from Zika disease. (Credit: Huy Mach)
Scientists have zeroed in on an antibody that could effectively treat the Zika virus in both adults and fetuses.
Researchers at Washington University School of Medicine in St. Louis and Vanderbilt University School of Medicine have identified a human antibody for Zika that has proven effective for both adult mice and fetus mice and will now do more studies to ensure the antibody will effectively fight the virus in humans.
Dr. Michael Diamond, the Herbert S. Gasser professor of Medicine and the study’s co-senior author, told R&D Magazine in an exclusive interview, adding that the research team will continue to study the antibody and how to utilize it to effectively treat Zika in humans.
“Of course our study was performed in mice — so we don’t know exactly how this will translate to humans,” Diamond said. “In the paper we were able to administer the antibody 24 hours after infection and completely protect the fetus.
“However, we are currently doing studies to see if this window can be extended and also investigate whether there are differences in the different stages of pregnancy. The key point is that this will need to be corroborated in humans to determine the effective window of treatment.”
Diamond, co-senior author Dr. James Crowe, and other colleagues screened 29 anti-Zika antibodies from people who had recovered from Zika infection and identified ZIKV-117 as the one antibody that efficiently neutralized in the lab five Zika strains.
“We feel it could be one avenue along with the development of vaccines, especially if there is a delay in getting vaccines to market,” Diamond said. “Also, targeting the mosquito is another important way to control Zika virus.”
Zika causes mild fevers and rashes in adults, but also can cause birth defects including microcephaly, intracranial calcifications and other brain or eye abnormalities.
The study included giving pregnant mice the antibody either one day before or one day after they were infected with the virus. In both cases, this resulted in the antibody treatment markedly reducing the levels of the virus in pregnant females and their fetuses, as well as in the placentas, compared with pregnant mice that did not get the treatment.
The placentas from the treated females appeared normal and healthy, unlike those from the untreated females, which showed destruction of the placental structure that can cause slow fetal growth or even fetal death.
The adult mice were also protected against a lethal dose of Zika, even when given the antibody five days after the initial infection.
Because Zika is rarely lethal in humans, scientists used a lethal dose in the mice test to see how well the antibody works under the most stringent conditions, which would provide evidence that antibodies can be the cheapest and simplest method to protect adults and fetuses from Zika.
There is also an outside possibility that a Zika vaccine could worsen symptoms in people who encounter the virus later, which occurs in the dengue virus, a close relative of Zika.
The researchers tested whether they could eliminate the possibility of antibody-dependent enhancement of Zika infection by modifying the antibody so it could not participate in the process, which proved to be just as effective as the original at protecting the placenta and the fetus.
Administering antibodies to pregnant women can protect fetuses by preventing the transmission of the virus from the other to fetus. A woman living in a Zika-epidemic area would receive the antibodies throughout her pregnancy, beginning when she first learns she’s pregnant, regardless as to whether or not they are diagnosed with Zika.
Co-senior author Crowe, of Vanderbilt, will now continue the process of developing the antibody as a potential therapeutic, ramping up production and laying the groundwork for human studies, while Diamond is focusing on determining whether antibodies could be used to clear persistent Zika infection.
The study was published on Nov. 7 in Nature.
Filed Under: Drug Discovery
