Timed control of immune sensor activation and RNA delivery separates antibody and cell immune responses

Co-administering a polymeric STING agonist prodrug with a specific formulation of mRNA vaccine resulted in decreased antigen-specific adaptive type 1 responses.

• Targeting the STING agonist to antigen-presenting cells may enhance vaccine responses without limiting mRNA expression.
• Mismatched timing of type I interferon and antigen expression could negatively impact adaptive immune responses.
• Synchronizing delivery of lipid nanoparticle mRNA and STING signaling led to increased type 1 T cell responses.
• The improved immune response did not affect humoral immunity and redirected immune skewing.
• Enhanced protection against pulmonary Acinetobacter baumannii was observed with the synchronized delivery strategy.

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