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Enhancing mRNA-lipid nanoparticle vaccine-induced T cell responses by simple supplementation with class B CpG
Haruki Hirata1, Yasuhiro Abe2, Yasushi Itoh3
1Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Abstract:
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.
