DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

mRNA-based vaccines make a step forward because the SARS-CoV-2 pandemic and therefore are presently accustomed to develop anti-infectious therapies. If selecting a delivery system as well as an enhanced mRNA sequence are a couple of important aspects to achieve in vivo effectiveness, the perfect administration route for individuals vaccines remains unclear. We investigated the influence of fat components and immunization route concerning the intensity and excellence of humoral immune responses in rodents. The immunogenicity of Aids-p55Gag encoded mRNA encapsulated into D-Lin-MC3-DMA or GenVoy-ionizable fat-based LNPs was compared after intramuscular or subcutaneous routes. Three consecutive mRNA vaccines were administrated adopted with a heterologous boost made up of p24-Aids protein antigen. Despite equivalent IgG kinetic profiles of general humoral responses, IgG1/IgG2a ratio analysis demonstrated a Th2/Th1 balance toward a Th1-biased cellular immune response when both LNPs were administrated through the intramuscular route. Surprisingly, a Th2-biased antibody immunity was observed when DLin-that contains vaccine was injected subcutaneously. A protein-based vaccine boost made an appearance to reverse this D-Lin-MC3-DMA good balance to a cellular-biased response correlated to a rise in antibody avidity. Our finding shows that the intrinsic adjuvant aftereffect of ionizable lipids seems to become determined by the delivery route used, that could apply to achieve potent and lengthy-lasting immunity after mRNA-based immunization.