Human Antibody Confers Protection Against Zika Virus Infection in Fetal Mice

Highlights

• Zika virus can pass from an infected pregnant woman to her fetus through the placenta.
• Zika virus infection of the fetus can lead to birth defects affecting the brain including an abnormally small head (microcephaly), and other severe conditions.
• At present, there are no vaccines or medications to protect against Zika infection.
• Researchers have found a human antibody that protects developing mice from Zika virus infection.

Human antibody has been shown to protect developing fetal mice from the devastating effects of Zika virus infection, according to researchers at Washington University School of Medicine in St. Louis and Vanderbilt University School of Medicine. Aim of the Study
Currently there is no effective treatment for Zika virus infection either in the form of vaccines or drugs. The study authors wished to test if an antibody isolated from humans known to have suffered from the infection could protect developing fetal mice against Zika virus infection.

Details of the Study

The researchers isolated an antibody from the blood of persons known to have had Zika virus infection previously.

The antibody, nicknamed ZIKV-117M, was found to neutralize all lab strains of the virus tested, namely the African, Asian and American types, covering the global diversity of the virus.

Next, the authors wished to test the efficacy of the ZIKV-117 antibody in pregnant mice and protection of developing fetal mice against the effects of the virus. To this end, the antibody was given to pregnant mice either one day prior to or one day after being infected with the virus.

Findings of the Study

Advertisement

The results of the study included the following The antibody was shown to reduce levels of virus in pregnant mice, their fetuses and the placenta, compared to pregnant mice that were not administered the antibody. Damage to the placenta is known to cause growth retardation, and even fetal death, both of which have been described in Zika virus infections in pregnant women.

"We did not see any damage to the fetal blood vessels, thinning of the placenta or any growth restriction in the fetuses of the antibody-treated mice," said co-author Indira Mysorekar, PhD, an associate professor of obstetrics and gynecology, and of pathology and immunology at Washington University, and co-director of the University's Center for Reproductive Sciences. "The anti-Zika antibodies are able to keep the fetus safe from harm by blocking the virus from crossing the placenta."

Advertisement

Further, the antibody ZIKV-117 was also seen to improve chances of survival in male mice that received the antibody, compared to those that did not, implying that the antibody might help combat active infection as well.

The researchers deliberately administered a lethal dose of the virus to the male mice to test how effective the antibody was in stringent and extreme conditions. The antibody passed the test with flying colors, even when given five days after the initial infection.

"We stacked the deck against ourselves by using a highly pathogenic strain of Zika, and even in that case, the antibody protected the mice," said Diamond, who is also a professor of pathology and immunology, and of molecular microbiology.

The authors claim that the naturally occurring antibodies isolated from humans represent the first instance of any medical intervention that has prevented Zika virus infection and fetal damage.

Scope of the Study Findings

• The findings of the study prove that antibodies alone can confer protection in adults and developing fetuses from Zika.
• It also indicates that a vaccine that could elicit protective antibodies in women also may protect their fetuses in ongoing as well as future pregnancies. A vaccine might be the cheapest and ideal way to prevent Zika related birth defects.
• A vaccine currently undergoing human trials, has not been tested yet in pregnant animals. This new study provides strong evidence that it could be effective in protecting fetuses as well.
• Until a vaccine becomes available, antibodies administered to pregnant women might be effective in protecting their fetus. It is suggested that a woman in a Zika-endemic area could be given the antibodies throughout her pregnancy, irrespective of whether she has been infected or not.

Testing for Antibody Dependent Enhancement – A Possible Pitfall of Zika Vaccine

There is a small but definite possibility that a Zika vaccine could cause serious illness in people who encounter the virus later. This has been seen with dengue virus, a close relative of Zika.

People who already have antibodies against one strain of dengue virus get severe illness if infected with a second strain of the virus later. The phenomenon, termed antibody-dependent enhancement, has been seen with Zika virus in a petri dish (in vitro) but never been described in animals or in epidemiologic surveys of people living in Zika-endemic areas.

The researchers also tested if they could eliminate the chance of antibody-dependent enhancement by altering the antibody so it could not participate in the process. The modified antibody proved to be equally effective in protecting the placenta and fetus as the original antibody.

Future Research Plans

• The authors are in the process of developing the antibody as a potential therapeutic, and laying the foundation for human studies.
• Additionally, they are keen on determining if these antibodies might be effective in clearing persistent Zika infection.

"We know that Zika can persist in certain parts of the body, such as the eyes and the testes, where it can cause long-term damage, at least in mice," Diamond said. "We showed that the antibody can prevent disease, and now we want to know whether it can clear persistent infection from those parts of the body."

References

1. Zika Virus - (https://www.cdc.gov/zika/pregnancy/)

Source-Medindia