Essential Role of T Cells in Shielding Children from Severe Dengue Infections Identified

Children who encounter multiple dengue virus infections develop a robust army of T cells designed to combat the virus, according to new research led by scientists at La Jolla Institute for Immunology (LJI). The findings, recently published in JCI Insights, indicate that these T cells play a crucial role in developing immunity against the dengue virus. In fact, most children who have experienced two or more dengue infections show only minor symptoms—or even none—when they contract the virus again.

“We saw a significant T cell response in children who had been infected multiple times,” says Daniela Weiskopf, Ph.D., lead author of the study and an LJI Assistant Professor. Dengue virus affects up to 400 million people annually, with limited vaccines available for any of its four species, or “serotypes.”

The researchers hope their findings will guide the development of a dengue vaccine that triggers such a strong T cell response. The research comes at a time when mosquito populations capable of spreading dengue are expanding into new regions, including Southern California.

In 2023, health officials in California reported the state’s first-ever locally acquired case of dengue virus. Since then, Los Angeles County has recorded 12 additional cases and San Diego County has confirmed two more local infections. “Dengue is moving into areas where most people have never encountered it,” says Weiskopf, who is a member of LJI’s Center for Vaccine Innovation.

Understanding T cells’ role in fighting dengue

Weiskopf and her team aimed to determine how T cells impact the severity of dengue virus infections. Are they beneficial or detrimental? A weak response can make it difficult to fight infection, while an overly robust one may cause harmful inflammation that could lead to fatal complications.

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

These children, aged between 2 and 17 years old, have regular blood tests to check for antibodies against the dengue virus. An increase in these antibodies compared to previous measurements indicates a past infection. The researchers can also detect asymptomatic cases of dengue using the blood test, where exposure has occurred without visible symptoms.

The team found that the number of T cells specifically targeting dengue increases with each infection and appears to be beneficial for pediatric patients. Children who have had two or more infections are less likely to show clinical symptoms if they contract the virus again, while those infected only once are more prone to exhibit disease symptoms during a subsequent infection.

Next steps in developing life-saving vaccines

The new research may explain why recent dengue vaccine trials showed safety and efficacy in some patients but not others. The vaccine called Dengvaxia was approved by the FDA for children aged 9-16 who live in endemic areas, assuming they had previously been exposed to the virus.

Further licensing required an antigen test to prove previous exposure, as the vaccine did not work if a person hadn’t encountered dengue before. Could it be that their T cells weren’t prepared? As this study suggests, multiple exposures might be needed for immunity to develop fully.

“There’s still a lot of work ahead,” says Weiskopf regarding harnessing T cells against the virus.

Additional authors of the study, “Frequency of Dengue Virus-Specific T Cells is related to Infection Outcome in Endemic Settings,” include Rosa Isela Gálvez, Amparo Martínez-Pérez, E. Alexandar Escarrega, Tulika Singh, José Víctor Zambrana, and Ángel Balmaseda.