Chronological Management of Adjuvant Effect for Optimized mRNA Vaccine Inspired by Natural Virus Infection.
basic_science · Level V
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- Record sourced from PubMed, PMID 39011561.
- Also identified by DOI 10.1021/acsnano.4c04953.
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Abstract
The efficacy and safety of mRNA vaccines both rely on a fine-tuning of specific humoral and cellular immune responses. Instead of adjustments in vaccine component, we proposed a concept of chronological management of adjuvant effect to modulate the adaptive immune potency and preference inspired by natural virus infection. By simulating type I interferon expression dynamics during viral infection, three vaccine strategies employing distinct exposure sequences of adjuvant and mRNA have been developed, namely <b><i>Precede</i></b>, <b><i>Coincide</i></b>, and <b><i>Follow</i></b>. <b><i>Follow</i></b>, the strategy of adjuvant administration following mRNA, effectively suppressed tumor progression, which was attributed to enhanced mRNA translation, augmented p-MHC I expression, and elevated CD8<sup>+</sup> T cell response. Meanwhile, <b><i>Follow</i></b> exhibited improved biosafety, characterized by reduced incidences of cardiac and liver toxicity, owing to its alteration to the vaccination microenvironment between successive injections. Our strategy highlights the importance of fine-tuning adjuvant effect dynamics in optimizing mRNA vaccines for clinical application.