P27.06
Background: DNA vaccines are an important approach for the generation of humoral and cellular immune responses in vivo. We have recently reported that combining an IL-12 expression vector along with HIV DNA encoded antigens can induce robust T cell responses in the clinic (HVTN 080). Identification of novel adjuvants at the innate to adaptive immune border will likely provide further improvements in DNA vaccine potency. In this regard we have recently developed a novel alarmin IL-33 as a new immunoadjuvant in the synthetic EP delivered DNA vaccine platform. We hypothesized that this endothelial cell alarmin would be in a particularly effective position to transition the adaptive immune response after viral infection.
Methods: Mice were immunized with immune plasmid adjuvant IL33 in combination with DNA followed by EP two to three times at three week intervals. One week post final vaccination, spenocytes were harvested to investigate cellular responses.
Results: We report that IL-33 is capable of enhancing potent antigen (Ag)-specific effector and has a similar robust effect on enhancing memory T cell immunity in vivo in a DNA vaccine setting. Additionally, IL-33 augmented vaccine-induced Ag-specific polyfunctional CD4+ and CD8+ T cell responses. Importantly a large proportion of CD8+ T cells undergo cytolytic plurifunctional degranulation that is improved over DNA vaccine alone. We show that IL-33 can particularly expand the magnitude of Ag-specific CD8+ T cell responses and elicit stronger and longer lived effector-memory CD8+ T cells. For HIV antigens, both the magnitude as well as the phenotype of T cells induced by the IL-33 DNA vaccine are improved.
Conclusions: We have now developed a Rhesus IL-33 genetic adjuvant for studies in NHP which allow for more detailed studies including challenges to be performed. These studies will be informative for HIV vaccine development and lay the groundwork for this novel genetic adjuvant for study in the HIV vaccine setting.
