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bioRxiv · 10.1101/2024.03.01.582992

Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation

Sanchez, S.·Dangi, T.·Awakoaiye, B.·Irani, N.·Fourati, S.·Richner, J. M.·Penaloza-MacMaster, P.
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Abstract

mRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines.

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Sanchez, S., Dangi, T., Awakoaiye, B., Irani, N., Fourati, S., Richner, J. M., Penaloza-MacMaster, P.. 2024-03-04. Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation. https://doi.org/10.1101/2024.03.01.582992

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