Dengue-Fighting T-cells: LJI Scientists' Discovery

The Dangers of Dengue:

Dengue virus infects up to 400 million people each year, and there are few vaccines and no approved therapies available for any of the four species, or "serotypes," of the virus.

Weiskopf and her colleagues set out to understand how T cells might sway the severity of dengue virus infection.

Are T cells helping or hurting young patients?

The immune system has to strike a careful balance when fighting viruses. A weak T cell response makes it tough to fight infection. On the other hand, an overzealous T cell response can cause harmful inflammation and potentially fatal complications.

The researchers studied a group of 71 children in Managua, Nicaragua, a region where dengue virus is endemic. Since 2004, study co-author Eva Harris, Ph.D., Director of the Center for Global Public Health at UC Berkeley, has worked with Nicaraguan scientists to study dengue infections in this patient group.

The findings, published recently in JCI Insights, suggest that these T cells are key to dengue virus immunity. In fact, most children who experienced two or more dengue infections showed very minor symptoms—or no symptoms at all—when they caught the virus again.

Meanwhile, children only infected once were more likely to show clinical symptoms of disease during a later infection.

These children, aged 2 to 17, come in for regular blood draws to test for antibodies against dengue virus. By detecting a rise in these antibodies, compared to the previous year, researchers can tell if a child has dealt with a past dengue virus infection. Importantly, researchers can also use the blood test to catch inapparent cases of dengue infection—where a child has been exposed to the virus but is showing no clinical symptoms.

The researchers found that the number of dengue-fighting T cells in these children builds up with each infection, and these T cells appeared to be helping the pediatric patients. 

The new study may offer context for why a recent dengue virus vaccine, called Dengvaxia, appeared safe and effective in just a subset of patients at risk for dengue infection. The vaccine was only FDA-approved for children who were ages 9 to 16—and lived in a dengue-endemic area, assuming that they have experienced dengue infection by that age. Subsequent licensure in other countries required an antigen test to prove previous exposure.

The vaccine didn't work if a person hadn't been exposed to dengue virus before. Could it be that their T cells weren't ready to jump into action?

As the new study suggests, it may take multiple dengue virus exposures to gain immunity. Weiskopf says scientists will continue to investigate how to harness T cells to fight dengue virus.

References:

1) Gálvez, Rosa Isela, Amparo Martínez-Pérez, E. Alexandar Escarrega, Tulika Singh, José Victor Zambrana, Ángel Balmaseda, Eva Harris, and Daniela Weiskopf. 2 2025. “Frequency of Dengue Virus–Specific T Cells Is Related to Infection Outcome in Endemic Settings.” JCI Insight 10 (4). https://doi.org/10.1172/jci.insight.179771.

(Newswise/SD)