Dengue is a mosquito-borne disease which is a continually expanding global issue caused by four closely related dengue viruses. The dengue virus, present in four distinct serotypes, infects up to 280-500 million individuals annually around the world. Though many recover quickly from the dengue infection, around 500,000 of the infected develop severe dengue disease, a condition that has a 2.5 per cent mortality rate.
Now, a team led by the Walter Reed Army Institute of Research has gained new insights into the mechanism of vaccine-induced T cell immunity utilizing single-cell RNA sequencing and metabolic profiling techniques, which may help combat the dengue virus.
The study, published in Nature Communications, was conducted at the WRAIR Viral Diseases Branch in partnership with the Department of Cell and Molecular Biology, Institute for Immunology and Informatics at the University of Rhode Island.
The study utilized samples from a Phase 1 clinical trial for TAK-003, a live-attenuated tetravalent dengue vaccine.
According to researchers, if a patient experiences dengue infection from one serotype and is then re-infected with a distinct dengue serotype, the likelihood of developing severe dengue increases significantly.
This, in turn, complicates the development of a dengue vaccine, which needs to induce a protective response against all four stereotypes and ensure that severe dengue is not caused by the vaccine. Thus, a healthy T cell response is considered to be a vital part of immunity to dengue and other viral diseases.
The TAK-003, developed to protect against all four serotypes, has been shown to be safe and immunogenic in small animal models and non-human primates. The study shed significant light into the regulation, gene expression and metabolic pathways of T cells, along with the discovery of a marker, transferrin receptor 1 (TfR1), to identify the differentiation potential of CD8+ cells, suggesting that T cell immunity is dependent on the availability of specific metabolites.
Speaking about the study, lead author Lt. Col. Richard Jarman said that the DoD Dengue Vaccine Program strived to understand mechanisms to enhance protection from diseases and that collaborative effort with a partner's vaccine suggests that targeting the unique metabolic requirements of the immune cells thought to provide protection from dengue infection may contribute in the establishment of protective immunity following vaccination.
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