Understanding the Critical Role of T Cells in Shielding Children Against Severe Dengue Infections

According to a new study led by scientists at the La Jolla Institute for Immunology (LJI), children who experience multiple cases of dengue virus develop an army of T cells dedicated to fighting the disease. The findings, published in JCI Insights, indicate that these T cells are crucial to dengue immunity. Specifically, most children with two or more dengue infections exhibited only minor symptoms—or none at all—when reinfected. “We observed a significant T cell response in children who had been infected multiple times,” says Daniela Weiskopf, Ph.D., the study leader and an LJI Assistant Professor.

Dengue virus affects up to 400 million people annually, with limited vaccines and no approved therapies for its four serotypes. The researchers hope that their findings will guide the development of a dengue vaccine capable of inducing a similar robust T cell response. This research comes at a critical time as mosquitoes carrying the virus are expanding into new territories, including Southern California.

Health officials in California reported the state’s first locally acquired dengue case in 2023. Since then, Los Angeles and San Diego counties have confirmed additional cases of local acquisition. “Dengue is spreading to regions where most people have never encountered it,” says Weiskopf, who is a member of LJI’s Center for Vaccine Innovation. “This will significantly change the landscape.”

T cells play a pivotal role in fighting dengue virus infection. While weak T cell responses struggle against infections, overly aggressive ones can lead to harmful inflammation and potentially life-threatening complications. To investigate this balance, Weiskopf and her team studied 71 children aged 2 to 17 in Managua, Nicaragua—a region where the virus is endemic.

Collaborating with Nicaraguan scientists since 2004, study co-author Eva Harris, Ph.D., Director of the Center for Global Public Health at UC Berkeley, has focused on dengue infections among this patient group. These children undergo regular blood tests to detect antibodies against the virus. A rise in these antibodies compared to previous years indicates past infection, while tests can also identify asymptomatic cases.

The researchers found that T cell numbers increase with each subsequent dengue infection, and these cells appeared beneficial for pediatric patients. Children with a history of two or more infections were less likely to show clinical symptoms upon reinfection, whereas those infected once showed higher likelihoods of disease severity in future exposures.

This study provides context for the recent Dengvaxia vaccine’s mixed results. FDA-approved only for children aged 9-16 living in dengue-endemic areas who have had prior exposure, it highlighted that the T cell response might be critical to effective vaccination. Subsequent approvals required proof of previous infection using an antigen test.

As further research explores ways to harness T cells against dengue virus, Weiskopf emphasizes ongoing efforts. “There is still much work to be done,” she says.

Additional study authors include Rosa Isela Gálvez, Amparo Martínez-Pérez, E. Alexandar Escarrega, Tulika Singh, José Víctor Zambrana, and Ángel Balmaseda.