Characterization of distinct immune responses induced by mRNA, viral vector, and protein subunit vaccines 4455

Abstract Description The COVID-19 pandemic has accelerated the development of diverse platform-based vaccines, each characterized by distinct immunogenicity and efficacy profiles in humans, necessitating comprehensive immunological comparisons. This study investigated the immune responses induced by key vaccine platforms— mRNA, viral vector, and protein subunit vaccines— expressing ovalbumin (Ova) in mice. Vaccination with Ova mRNA-LNP produced strong Ova-specific IgG and CD8 T cell responses, both in magnitude and cytokine production, particularly after the second dose. Adenovirus serotype 5 (Ad5)-Ova elicited a robust CD8 T cell response and the highest OVA-specific IgG response alongside elevated T follicular helper (Tfh) cells following the primary vaccination. However, a second dose of Ad5 resulted in minimal enhancement of these responses. Interestingly, Ova mixed with empty lipid nanoparticles (eLNP) generated IgG levels comparable to those induced by mRNA-LNP vaccination. However, its CD8 T cell response was lower than that elicited by mRNA-LNP or Ad5 but exceeded that from emulsion-adjuvanted Ova. Moreover, distinct patterns and kinetics of innate immune cell activation were observed across vaccine platforms, with mRNA-LNP and Ad5 exhibiting the most distinct transcriptomic profiles during the innate immune response. These findings highlight the unique mechanisms of action associated with different vaccine platforms and offer insights for optimizing vaccine design against pathogens. Funding Sources Supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (RS-2024-00439160). Topic Categories Vaccines and Immunotherapy (VAC)