An unusual type of antibody that even at minuscule levels neutralizes Zika virus and renders infection with the virus undetectable in preclinical models has been identified by a team led by Weill Cornell Medicine, NewYork-Presbyterian and National Institutes of Health (NIH).
Since Zika can cause birth defects when passed from a pregnant woman to her fetus, this discovery could lead to the development of treatments to protect children from the disease’s potentially devastating effects.
In a paper published November 18 in Cell, researchers isolated a highly active immunoglobulin M (IgM) antibody – ; five-armed virus-binding immune protein; using blood cells from pregnant women infected with Zika. In experiments on mice, they determined that the antibody not only protected the animals from fatal infection, but also inhibited the virus to the point where it could not be detected in their blood.
Zika virus is currently circulating at low levels in many tropical countries, but that will inevitably change, according to co-author Dr. Sally Permar, MD, Nancy C. Paduanu Professor of Pediatrics and chief of pediatrics at Weill Cornell Medicine and pediatrician in chief at NewYork-Presbyterian/Weill Center. Cornell Medical and NewYork-Presbyterian Komansky Children’s Hospital. Dr. Mattia Bonsignori, chief of the translational immunobiology unit in the Infectious Diseases Laboratory, National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, co-author.
What is important is that we must be prepared for another Zika virus outbreak.”
Dr. Sally Bermar, MD, Nancy C. Paduano Professor of Pediatrics and chief of pediatrics at Weill Cornell Medicine
At this point, doctors have no approved vaccines or treatments to offer patients. With further research, this antibody has the potential to help bridge that gap, according to Dr. Permar. “There are two potential approaches that could be used: rapid reduction of Zika levels in the blood of infected pregnant women, or as a preventive measure given to those at high risk of contracting the virus during an outbreak.”
Zika virus is transmitted by infected Aedes aegypti mosquitoes, and usually causes a mild illness in adults. However, Zika virus infection in pregnant women can cause serious birth defects, including abnormally small head size and brain damage in their babies.
During the Zika virus outbreak that began in 2015, researchers in Brazil led by co-authors Dr. Reynaldo Dietz, of Global Health, Tropical Medicine and Federal University of Espírito Santo, and Dr. Camila Gioberti, also of the Federal University of Espírito Santo, took blood samples from infected pregnant women. . The team decided to focus on those who had been infected with the Zika virus but had given birth to babies who appeared healthy, because they suspected that these patients might harbor antibodies capable of preventing congenital infection.
One of these patients gave birth to an apparently healthy baby even after Zika was detected in their blood for about two months, which was an unusually long time. The lab teams, led by first author Dr. B cells produced an IgM antibody with a strong ability to block viral particles from invading cells.
The identity of this antibody, called DH1017.IgM, surprised investigators because it belongs to a typical, weaker, less mature type of antibody that is produced early in infection. However, in this case, the effective function of this antibody depends on it being an IgM antibody. When the collaborators examined its molecular structure upon binding to a virus, they found that multiple arms could attach to a viral particle at once. The findings suggest that IgM antibodies may be particularly effective for protecting against Zika virus and possibly other viruses, the authors suggest.
To develop the antibody into a treatment, the researchers plan to begin testing its safety and how effectively it prevents transmission to the fetus in additional preclinical models. Recalling how pregnant women were excluded from COVID-19 vaccine trials, Dr. Permar emphasized that when human studies of new preventive or curative treatments for Zika virus are conducted, they should be included. “Pregnant women are the population who need vaccines or immunotherapies against Zika,” she said. “It is essential to roll out safe Zika vaccines and treatments during pregnancy as soon as there is evidence of an outbreak.”
This research was supported by NIAID grant R21-AI123677.
Singh, T.; et al. (2022) IgM specific for Zika virus during pregnancy shows highly effective neutralization. cell. doi.org/10.1016/j.cell.2022.10.023.