Antibody protects pregnant mice & their fetuses from Zika virus infection

A team of scientists from Vanderbilt University Medical Center and Washington University School of Medicine in St. Louis have identified a human monoclonal antibody able to protect pregnant mice and their developing fetuses from Zika virus infection.

Dr. James Crowe Jr., director of the Vanderbilt Vaccine Center and co-senior author of the recent Zika paper. Photo courtesy of Vanderbilt University Medical Center.

Dr. James Crowe Jr., director of the Vanderbilt Vaccine Center and co-senior author of the recent Zika paper. Photo courtesy of Vanderbilt University Medical Center.

The research, published in November in Nature, was led by a Kerafast providing investigator from Vanderbilt University, co-senior author Dr. James Crowe, Jr. The Crowe lab studies viral immunology and cell biology, aiming to discover mechanisms important to the development of new vaccines. As part of this research, the team developed a highly efficient method to isolate human monoclonal antibodies able to neutralize viruses ranging from Ebola to HIV. Their CD40L Expressing Feeder Cell Line, used to generate B cell cultures yielding human monoclonal antibodies, is available via the Kerafast platform. At the start of the Zika virus outbreak, the Crowe lab leveraged their viral expertise to work toward better understanding, treating and vaccinating against Zika.

The mosquito-borne Zika virus emerged as a significant global health threat last year due to its ability to cause severe birth defects in children born to infected women. Researchers worldwide quickly turned their attention toward the previously little-studied Zika virus. During this time, the Crowe lab made its Zika Virus Envelope (E) Protein Antibody, a human serum specimen containing polyclonal antibodies induced by natural infection with Zika, available to the global scientific community via the Kerafast platform.

A flurry of research papers have been published since the emergence of Zika as a public health threat, and a vaccine is currently in human trials. However, there is currently no treatment available to prevent maternal-to-fetal transmission of the virus. The recent Nature paper provides a promising new therapeutic lead.

ZIKV-117 antibody: new therapeutic target?

In the new study, the researchers isolated antibodies from the blood of people who had previously been infected with Zika virus. The antibodies reacted to the envelope, or E, protein on the surface of the virus. The team then screened 29 of these antibodies and found one, called ZIKV-117, which broadly neutralized several different strains of the virus.

The researchers gave ZIKV-117 to pregnant mice either one day before or after infection with the Zika virus. In both scenarios, injection of the antibody “markedly reduced” disease and mortality in the adult mice and their fetuses. In addition, placentas in the treated mice appeared healthy, while those in untreated mice were damaged. The antibody also protected adult male mice against a lethal dose of the Zika virus, even when given five days after the initial infection.

“These naturally occurring human antibodies isolated from humans represent the first medical intervention that prevents Zika infection and damage to fetuses,” said Dr. Crowe in a press release. “We’re excited because the data suggests we may have antibody treatments in hand that could be developed for use in pregnant women.”

The researchers caution that similar studies need to be conducted in primates before moving onto human trials. However, they are hopeful ZIKV-117 could eventually be developed as a protective antibody treatment for pregnant woman at risk of Zika infection, as well as aid in efforts to develop an effective Zika vaccine.

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