Dengue virus (DENV) is responsible for growing numbers of infections worldwide, and has proven a significant challenge for vaccine development. Previously we demonstrated that CD8(+) T cell responses elicited by a dengue live attenuated vaccine resemble those observed by natural infection. In this study we screen PBMCs from donors vaccinated with a tetravalent live attenuated dengue vaccine (TV005) with pools of dengue virus derived predicted MHC class II binding peptides. The definition of CD4(+) T cell responses after live vaccination is important as CD4(+) T cells are known contributors to host immunity including cytokine production, help for CD8(+) T- and B- cells, and direct cytotoxicity against infected cells. While responses to all antigens were observed, DENV specific CD4(+) T cells were predominantly focused on the capsid and non-structural NS3 and NS5 antigens. Importantly, CD4(+) T cell responses in vaccinees were similar in magnitude and breadth when compared to natural infection, recognized the same antigen hierarchy and had similar profiles of HLA restriction. We conclude that TV005 vaccination has the capacity to elicit CD4(+) responses closely mirroring those observed in a population associated with natural immunity.
The development of effective vaccination strategies against dengue virus infection is of high global public health interest. Here we study the CD4 T cell response elicited by a live attenuated tetravalent vaccine and show that they resemble responses seen in humans naturally exposed to dengue virus. This is an important issue since it is likely that optimal immunity induced by a vaccine require induction of CD4 response against the same antigens recognized as dominant in natural infection. Detailed knowledge of the T cell response may further contribute to the identification of robust correlates of protection against dengue virus.