Lipid nanoparticle (LNP) components dictate the cellular immune responses to vaccination 3550

Description The type of cellular immune response elicited by a vaccination is key to determination of the success of that vaccination. Historical vaccines have comprised largely of attenuated pathogen or large portions of the pathogen complexed with adjuvant, and most of the data around vaccines focuses on IgG antibody responses to the pathogen. Recent advances in mRNA and lipid nanoparticle (LNP) technology have been instrumental in controlling the worldwide SARS-CoV-2 pandemic and show promise for utility in developing vaccines for many common pathogens. A significant portion of the effort to develop new LNP vaccines uses protein expression levels as a surrogate or prerequisite for immune stimulation, but expression of target antigen is not the only factor to consider. In this study, we formulated LNPs with SARS-CoV-2 Spike mRNA as a model antigen. The LNPs were based on established ionizable lipids, and some included putative adjuvants as additional components of the LNPs. A cohort of mice was immunized, and immune responses were assessed by ELISA for total and neutralizing antibody production, flow cytometry for T cell subsets, and ELIspot for Spike peptide-specific immune responses. We found that the different LNP formulations stimulated different aspects of the immune response, which can inform future approaches to vaccine development.