Unusual Zika virus-specific antibody exhibits ultrapotent neutralization

An unusual type of antibody that neutralizes the Zika virus at even low levels and undetects virus infection in preclinical models has been identified by a team led by Weill Cornell Medicine, New York-Presbyterian and National Institutes of Health (NIH) investigators.

Because Zika can cause birth defects when it is passed from a pregnant person to their fetus, the discovery could lead to the development of therapies to protect babies from the disease’s potentially devastating effects.

In research published Nov. 18 in Cell, investigators isolated an ultrapotent immunoglobulin M (IgM) antibody -; A five-armed immune protein that attaches to viruses-; Zika uses blood cells taken from infected pregnant people. In experiments with mice, they determined that the antibody not only protected the animals from an otherwise lethal infection, but suppressed the virus so that it was undetectable in their blood.

Zika is currently spreading at low levels in many tropical countries, but that will inevitably change, according to co-senior author Dr. Sally Parmer, Nancy C. Paduano Professor in Pediatrics and Chair of Pediatrics at Weill Cornell Medicine and Chief of Pediatrics at NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian Komansky Children’s Hospital. Dr. Mattia Bonsignori, chief of the Translational Immunobiology Unit at the National Institute of Allergy and Infectious Diseases (NIAID) Laboratory, part of the NIH, is a co-senior author.

The important thing is that we have to be prepared for another outbreak of Zika.”


Dr. Sally Parmer, Nancy C. of Pediatrics. Paduano Professor and Chair of Pediatrics at Weill Cornell Medicine

At this point, doctors have no approved vaccines or treatments to offer patients. According to Dr. Parmer, with further research, this antibody has the potential to help fill that gap. “It could be used in two possible ways: to rapidly reduce blood levels of Zika in infected pregnant women, or as a preventive measure for those at risk of contracting the virus during an outbreak.”

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Transmitted by infected Aedes aegypti mosquitoes, the Zika virus usually causes a mild illness in adults. However, Zika virus infection in pregnant people can cause severe birth defects in their babies, including abnormally small heads and brain damage.

During the Zika outbreak that began in 2015, researchers led by co-authors Dr. Reynaldo Dietze of Global Health and Tropical Medicine and Federal University of Espirito Santo and Dr. Camila Guiberti of the Federal University of Santo, Santo, collected blood samples from pregnant individuals who had the infection. The team decided to focus on those who had been infected with Zika, but had given birth to healthy babies, because they suspected that these patients might have antibodies capable of preventing congenital infection.

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One of these patients gave birth to an apparently healthy baby even after Zika was detected in their blood for nearly two months, an unusually long time. Former graduate student at Duke University Medical Center, where Dr. Parmar’s lab was located for part of this research and laboratory teams led by first author Dr. Tulika Singh, now a postdoctoral fellow at the University of California, Berkeley, found that their B cells produced an IgM antibody with a strong ability to prevent viral particles from invading cells.

The identity of this antibody, called DH1017.IgM, surprised the investigators because it usually belongs to a weaker, less mature type of antibody that is produced early in the course of infection. However, in this case, the strong efficacy of this antibody depends on it being an IgM antibody. When the collaborators examined the molecular structure of the virus as it binds, they found that multiple arms can latch onto a single viral particle simultaneously. The study suggests that IgM antibodies may be particularly effective in protecting against Zika virus and possibly other viruses, the authors suggest.

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To develop the antibody into a therapy, the researchers plan to begin testing its safety and how effectively it can prevent infection in a fetus in additional preclinical models. Recalling how pregnant women were excluded from the COVID-19 vaccine trial, Dr. Parmar emphasized that when human studies are conducted for new preventive or therapeutic treatments for Zika, they must be included. “Pregnant people are the exact population that needs vaccines or immunotherapy for Zika,” he said. “It is critical that anti-Zika vaccines and therapies that are safe in pregnancy be introduced as soon as there is evidence of an outbreak.”

This research was supported by NIAID grant R21-AI123677.

Source:

Journal Reference:

Singh, T., etc (2022) A Zika virus-specific IgM expressed during pregnancy exhibits ultra-strong neutralization. cell doi.org/10.1016/j.cell.2022.10.023

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