Sandra Bos, PhD, MPH, research assistant professor in the Department of Infectious Diseases and Microbiology at Pitt Public Health, is helping reshape scientists’ understanding of immunity following dengue infection.
Published in Nature Communications, Bos’s study provides a comprehensive analysis of how antibody responses evolve after dengue infection, revealing that different antibody populations change over time in ways researchers did not expect.
Dengue—often dubbed “break-bone fever”—is a mosquito-borne illness found in tropical and subtropical regions that causes fever, flu-like symptoms, and intense joint and muscle aches. In severe cases, the illness triggers dengue hemorrhagic fever, a condition that can cause bleeding, a drop in blood pressure and death.
Bos, the study’s first author, said a major strength of the study was its use of samples from a long-running pediatric dengue cohort in Managua, Nicaragua.
“Because the cohort was so well characterized and the sampling was highly standardized, it provided an ideal foundation for this study,” she said. “Children can enter the study as soon as 1 year of age and are followed until age 16.”
Bos said the findings overturn several long-standing assumptions about dengue immunity. Researchers previously believed antibody levels gradually declined after primary infection while the overall composition of the immune response remained relatively stable.
“We found that some of these cross-reactive antibody populations—especially those that might be associated with future risk of severe dengue—actually increase over time,” she said. “In areas where dengue is endemic, repeated mosquito exposures may provide small immune boosts without causing illness, allowing these antibody populations to increase.”
Researchers have long known that antibodies targeting different viral proteins can behave differently. This study, however, found that antibodies targeting different regions of the same viral protein can also follow distinct trajectories over time.
“This study shows that even antibodies binding to different regions of a single protein can have distinct dynamics, which fundamentally changes how researchers think about long-term immunity,” Bos said.
Bos said the findings provide a foundational reference for future dengue research.
“Our results provide the most detailed picture to date of how different antibody populations evolve after natural dengue infection and could help improve diagnostic tests by identifying antibody markers that better distinguish recent from past infections,” she said. “They also provide a new framework that researchers can use when studying immunity and evaluating vaccine-induced antibody responses.”
Additional authors include Aaron Graber, a Microbiology and Immunology PhD student at the University of Pittsburgh; Tulika Singh, PhD; José Victor Zambrana, PhD; Elias Duarte; Reinaldo Mercado-Hernandez; Julia Huffaker; Angel Balmaseda, MD; and Eva Harris, PhD, of the University of California, Berkeley, along with collaborators from the Sustainable Sciences Institute and the Nicaraguan Ministry of Health.
-Ava Dzurenda