Newly Discovered Antibody ‘Neutralizes’ Zika Virus, Shows Mouse Study

A research team led by Vanderbilt University Medical Center scientist Prof. James Crowe, Jr., has isolated a human monoclonal antibody that in a mouse model ‘markedly reduced’ infection by the Zika virus.

Zika virus is a member of the Flavivirus genus in the Flaviviridae family. It was accidentally discovered in Uganda in 1947, during a course of surveillance on mosquitoes and primates.

Since a major outbreak was reported in Brazil last year, Zika infections have been reported throughout Africa, Asia, the Pacific, and the Americas.

During the past 15 years, Prof. Crowe and his colleagues have developed a high-efficiency method for isolating human monoclonal antibodies that has enabled to them identify neutralizing antibodies against a wide range of viral infections, from Ebola to HIV.

Monoclonal antibodies are made from a single clone of B cells, a type of white blood cell, that have been fused to myeloma cells to form fast-growing ‘hybridomas.’ This allows scientists to quickly generate large quantities of antibodies against specific viral targets.

In the current study, Prof. Crowe and co-authors from the Vanderbilt University Medical Center and the Washington University School of Medicine isolated 29 antibodies from the blood of three patients who had recovered from Zika infection. The antibodies reacted to the envelope or ‘E’ protein on the surface of the virus.

In cell culture studies, the team identified one, called ZIKV-117, that efficiently neutralized in the lab five Zika strains – corresponding to African, Asian, and American lineages.

Male mice that received a single dose of ZIKV-117 even five days after Zika infection were more likely to survive than those given a control antibody, suggesting that the antibody could treat active Zika infection.

The scientists next found that ZIKV-117 had protective effects during pregnancy.

Pregnant mice that received the antibody and were then infected with Zika virus had lower levels of the virus in their blood and brain tissues than mice not treated with ZIKV-117.

Among the treated mice, the team found protective levels of ZIKV-117 in fetal tissues and markedly reduced levels of virus in the placenta and the fetal brain.

Although more preclinical work is needed before establishing whether anti-Zika antibodies can reduce Zika complications and disease severity in humans, the results suggest that ZIKV-117 or similar antibodies could be developed to protect pregnant women and others.

In addition, the findings may inform the design of vaccines that elicit protective neutralizing antibodies against Zika virus.

“This is the first antiviral that has been shown to work in pregnancy to protect developing fetuses from Zika virus,” said study’s co-senior author Prof. Michael Diamond, from the Washington University School of Medicine.

“This is proof of principle that Zika virus during pregnancy is treatable, and we already have a human antibody that treats it, at least in mice.”

“These naturally occurring antibodies isolated from humans represent the first medical intervention that prevents Zika infection and damage to fetuses,” Prof. Crowe added.

“We’re excited because the data suggests we may have antibody treatments in hand that could be developed for use in pregnant women.”

“The remarkable potency and breadth of inhibition by ZIKV-117 has great promise as it was able to inhibit infection by strains from both Africa and America in cell culture and in animals, including during pregnancy,” Dr. Diamond said.

http://www.nature.com/nature/journal/vaap/ncurrent/full/nature20564.html

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