P41.25
Background: There has been great progress in understanding the detailed molecular mechanisms of HIV-1 infection but no effective vaccine has been developed to date. mRNA has emerged as a very promising new therapeutic agent in recent years and has already shown progress as an effective method for generating potent vaccines.
Methods: To create a vaccine with maximal potency, in vitro transcribed mRNAs were optimized for higher levels and extended translation by incorporation of selected UTRs, modified nucleosides, 5′ cap, 3′ poly(A)-tail, and other modifications and were HPLC-purified. To achieve both strong T cell and B cell responses, heterologous mRNA prime - protein boost vaccination regimens were used. For priming, naked mRNA encoding HIV envelope gp160 was administered intradermally into mice. Cell surface Env was used to increase exposure of neutralizing epitopes. Four weeks after the second mRNA prime, Env protein was injected intramuscularly as a boost. As nucleoside modified mRNA does not activate RNA sensors, to increase the robustness of the immune response, a series of adjuvant molecules and encoding mRNAs were co-injected along with the antigen-encoding mRNA. Flow cytometry and ELISA were used to evaluate T cell and B cell responses, respectively.
Results: Elevated levels of IFN-χ, TNF-α and IL-2 in antigen-specific CD4+ and CD8+ T cells and high gp120 antibody titers could be measured following two rounds of mRNA prime - protein boost vaccination.
Conclusions: Our results demonstrate that antigen-encoding nucleoside modified mRNA induces effective HIV-specific immune responses and has great potential for vaccination against infectious diseases.
