Abstract

mRNA vaccines have received full FDA approval to prevent COVID-19, and are being explored for multiple infectious diseases as well as cancer. While they have shown high efficacy at preventing severe disease caused by SARS-CoV-2, waning immunity has motivated the development of improved mRNA vaccine regimens. 4-1BB (also known as CD137) is a costimulatory receptor that has been shown to be important for T cell responses following viral infections and cancer. We asked whether triggering 4-1BB costimulation with agonistic antibodies could improve immune responses elicited by mRNA vaccines in C57BL/6 mice. Here, we show that triggering 4-1BB costimulation at the time of mRNA vaccination impairs CD8 T cell responses, whereas triggering 4-1BB costimulation after day 4 of mRNA vaccination improves CD8 T cell immune responses. These data demonstrate time-dependent effects of 4-1BB costimulation on cellular responses elicited by mRNA vaccines, and suggest that delayed provision of 4-1BB costimulation could offer immunologic benefits following mRNA vaccination.

This work was supported by a DP2 New Innovator Award to P.P.M.

This work was supported by a DP2 New Innovator Award to P.P.M.

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