Lipid nanoparticle-encapsulated microRNA-192: An anti-inflammatory adjuvant that enhances vaccine efficacy in aged mice.

Proinflammatory cytokines are essential for initiating immune responses; however, excessive or aging-related chronic inflammation impairs immunity and reduces vaccine efficacy. In this study, we developed lipid nanoparticles (LNPs) encapsulating anti-inflammatory microRNA-192 (miR-192) to attenuate inflammation and improve vaccine performance in the elderly. Results revealed that specific proinflammatory cytokines, including interleukin (IL)-6 and tumor necrosis factor (TNF)-α at the vaccination site, diminished antigen-specific antibody production. Notably, miR-192 endowed LNPs with strong anti-inflammatory properties, markedly enhancing vaccine efficacy, especially in aged mice. Transcriptomic analyses demonstrated that miR-192 downregulated multiple pro-inflammatory cytokines, such as senescence-associated secreted phenotype factors, which hinder vaccine responses. Additionally, miR-192 inhibited key components of the JAK-STAT signaling pathway, crucial for cytokine receptor signaling in myeloid cells. Overall, these findings indicate that miR-192 effectively suppresses harmful inflammatory responses, substantially enhancing vaccine efficacy, and highlight the therapeutic potential of the anti-inflammatory microRNA-based adjuvants for improving vaccination outcomes in the elderly.