Enhancing mRNA-lipid nanoparticle vaccine-induced T cell responses by simple supplementation with class B CpG oligodeoxynucleotides

mRNA-lipid nanoparticle (LNP) vaccines can elicit robust T cell responses; however, these responses remain insufficient, particularly in the context of cancer vaccine therapy. Although several types of adjuvants reportedly enhance T cell responses induced by mRNA-LNP vaccines, few comprehensive side-by-side comparisons exist, and it remains unclear which adjuvants are most suitable. Herein, we screened 15 adjuvants. The addition of class B CpG oligodeoxynucleotides (ODNs) markedly augmented T cell induction in an interleukin-12-dependent manner and promoted the antitumor effects of mRNA-LNP vaccines in mice. Class B CpG ODN-adjuvanted mRNA-LNP vaccines induced more potent T cell responses than the mRNA-LNP vaccine administered at a 10-fold higher dose, while exhibiting a more favorable safety profile. However, this approach also reduced the cellular uptake of mRNA-LNPs and antigen expression. As a possible mechanism underlying this reduced delivery efficiency, we found that class B CpG ODNs adsorbed onto LNPs and altered their particle characteristics. These findings demonstrate that supplementation with class B CpG ODN is a simple, safe, and readily implementable approach for enhancing mRNA-LNP vaccine-induced T cell responses. This study also highlights that adding auxiliary components to mRNA-LNPs can potentially affect the performance of LNPs as delivery carriers.

Abstract from PubMed (PMID 42933514). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.