Adjuvanted Protein Vaccines Boost RNA-Based Vaccines for Broader and More Potent Immune Responses.

: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but-due to limited breadth of the immune response-they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. : Specifically, four proprietary adjuvants (EmT4, LiT4Q, MiT4, and AlT4) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. : Results showed significant improvement in immune response strength and breadth-especially against more distant SARS-CoV-2 variants such as Omicron-when adjuvants were used in combination with boosters following an RNA vaccine prime. : The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity.