Pre-existing Immunity to Dengue and West Nile Viruses May Cause Increased Risk in Zika-Infected
{To watch a video of about the research, click here}
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.
The Zika virus is a member of the flavivirus family, as are dengue and West Nile. It was discovered in 1947 but remained relatively obscure until 2015, when a large outbreak occurred in Brazil and rapidly spread to other South and Central American countries. Today, the Zika virus is endemic to several U.S. territories, especially Puerto Rico, and active transmission has been reported in Florida and Texas. It is a significant public health concern because of the widespread outbreaks, the virus’s association with microcephaly and other neurological disorders, and its long-term persistence in human tissues—it can be sexually transmitted for months after the initial infection.
This study is the first to report a large-scale analysis of Zika virus enhancement by antibodies of individuals previously infected with the dengue and West Nile viruses. These findings raise urgent concern since the dengue and West Nile viruses are often endemic in Zika affected regions.
"Recent studies have shown that the Zika virus protein is structured similarly to that of dengue and West Nile," said the study’s co-author, Adolfo García-Sastre, PhD, Irene and Dr. Arthur M. Fishberg Professor of Medicine, Professor of Microbiology and Infectious Diseases, and Director of the Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai. “Our study is the first large-scale analysis of Zika virus enhancement in individuals infected with dengue and West Nile.”
Using blood samples from individuals infected with dengue and West Nile, researchers identified enhancement of Zika virus growth in cell cultures. The dengue- and West Nile-infected plasma was then administered to mice engineered to be susceptible to the Zika virus, resulting in increased mortality and morbidity, including fever and viral loads in the spinal cords and testes of the mice upon virus infection.
"We believe the antibody-dependent enhancement may explain the severe disease manifestations associated with recent Zika virus outbreaks, and highlights the need for great caution when designing vaccines for Zika and other flaviviruses," said co-author Jean Lim, PhD, Assistant Professor of Microbiology, Icahn School of Medicine at Mount Sinai. " Further understanding of pre-existing immunity is a high priority in the development of a vaccine that works."
“We found that the antibody-dependent enhancement effect was dependent on the dose of plasma administered,” said co-authorFlorian Krammer, PhD, Associate Professor of Microbiology, Icahn School of Medicine at Mount Sinai. “Low concentrations of cross-reactive antibodies clearly enhanced disease.”
The studies showed that high concentrations of dengue immune plasma resulted in protection against Zika infection, with 100 percent survival, no weight loss, and decreased symptoms. It was the lower concentrations that resulted in enhanced morbidity and mortality, highlighting that antibody-dependent enhancement is a particular worry in individuals with waning antibody levels.
The American Red Cross collaborated with the Mount Sinai team on this study.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.