Impact of pre-existing anti-replicase immunity on the efficacy of self-amplifying mRNA vaccines.

ABSTRACT: Self-amplifying mRNA vaccines use a viral replicase for self-amplification. It is currently unclear whether anti-replicase immunity occurs after saRNA vaccination, and whether such pre-existing anti-replicase immunity impacts the efficacy of subsequent saRNA vaccines. Using female mice, this study demonstrates that an initial saRNA vaccination schedule elicits replicase-specific immunity, which reduces the in vivo expression and impairs the Th1 cell responses of subsequent saRNA vaccines. Passive transfer experiments demonstrate that the suppression of T cell responses is driven by a synergistic effect of both anti-replicase antibodies and anti-replicase T cells. Interestingly, pre-existing anti-replicase immunity does not affect the ability of an influenza saRNA vaccine to provide full pr

SUBMITTER: Cui X 

PROVIDER: S-EPMC12783641 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature