Phenotyping of human immune responses to dengue vaccination and infection in Argentina

Latin America is currently experiencing the largest outbreak of dengue in its history. In the first months of 2024, there have been a total of 4,820,955 reported cases of dengue. This number is more than four times more than the number of cases reported during the same period in 2023, which itself was a record year with over 4.5 million cases. In the case of Argentina, mainly two serotypes are currently co-circulating (DENV2 58% and DENV1 42%). The recently approved Takeda Dengue vaccine (Qdenga) is now widely offered in Argentina. The Qdenga Dengue vaccine protects against all four serotypes of the dengue virus. Two vaccine doses are administered over a three-months interval.We propose to study the immune responses elicited by the Qdenga Dengue vaccine in naïve and previously infected individuals before and after the first and second vaccine doses. We will leverage approaches currently used in VIVA (e.g., multiplex chemokine/cytokine measurements [Luminex], high-dimensional cellular responses [AURORA flow cytometry], transcriptome analysis) to analyze responses to dengue vaccinations taking advantage of the introduction of dengue vaccines for the first time in Argentina. In addition, we will compare the results of our current studies with samples from the NIH tetravalent vaccine trials in Thailand (provided by Dr. Anna Durbin) to the data generated using samples from Qdenga vaccinees in Argentina. Lastly, we will recapitulate and dissect the Qdenga vaccine responses using the tonsillar histocultures model system.