Annually, June 15 is in fact designated International Anti-Dengue Day, an event usually unnoticed in the U.S. That may change, as dengue approaches our shores: over the last decades dengue-carrying mosquitoes expanded into Southern Europe and the U.S., and recently a cluster of cases was reported in Hawaii.

Fortunately, most infected individuals experience only mild flu. But some progress to a life-threatening hemorrhagic fever associated with dangerously low blood pressure and threat of shock. Currently, only mosquito control can prevent the infection: there is no dengue vaccine. Without one, the disease will likely remain a global health problem.

New Vaccine Design
Work by LJI’s Alessandro Sette, Ph.D., represents a new way of thinking about constructing a dengue vaccine. Previously, many vaccine biologists felt that evoking a strong antibody response on the part of the immune system’s B cells might be the optimal strategy. Sette has uncovered evidence that a robust T cell response will also be required to keep the virus in check.

He came to this conclusion after his lab studied blood samples of donors exposed to dengue virus in Sri Lanka. That analysis revealed sizeable numbers of cells called T helper memory cells, a T cell population that clearly “remembers” (and is ready for) infection. More intriguingly, donors infected with dengue multiple times showed a shift in T cell profile from helper T cells, which assist B cells in producing antibodies, to T cells resembling “T killers cells”, which can directly kill infected cells.

This exciting finding hints that factors that endow T cells with pathogen-killing rather than “helper” properties may block progression to the more deadly hemorrhagic form of the disease, and strongly suggests that an effective vaccine should contain elements that elicit this effect.

Testing New Vaccines and Antivirals
Sujan Shresta, Ph.D., is also a world authority on dengue virus. She is an expert in the creation of mouse models for the disease that serve as test platforms for dengue treatments. Moreover, many of Shresta’s mouse models have been used by pharmaceutical companies to evaluate potential vaccines or anti-viral compounds. One of the latter completely wipes out the virus in infected mice and is being evaluated in human trials. Shresta, herself, is also developing a novel dengue vaccine and drug candidates with maximal safety and efficacy.