Abstract 1916: Lymph node targeting double stranded CpG act effective adjuvant in cancer peptide vaccine

Background: Adjuvants can enhance immune responses of vaccinated antigen by inducing host innate immune responses. While cancer peptide vaccines were largely studied in recent years, effective cancer peptide vaccines have not been found yet so far because of their poor immunogenicity. Developing an effective vaccine adjuvant suitable for peptide antigen is a promising approach. CpG oligodeoxynucleotides(CpG) are a toll-like receptor 9 agonists and effectively elicit innate immune responses. In order to improve adjuvanticity of CpG, we designed a novel lymph-node targeting CpG, which is composed from a single stranded CpG and a modified complementary strand with amphiphilic chain. Methods: S-540956 is a double stranded oligodeoxynucleotide composed from a single stranded phosphorothioate oligonucleotide and the complementary strand with amphiphilic chain at the 5' end. Accumulating capability to lymph nodes of fluorescent labeled S-540956 was analyzed by flow cytometer, IVIS imaging system, and 2-photon microscopy. Incorporation of S-540956 by antigen-presenting cells in lymph nodes was assessed by Image Stream® imaging cytometer. To test cellular immune responses, three types of MHC class-I epitope peptides were employed as antigenic peptides. Therapeutic effect of S-540956 adjuvanted HPV E7 peptide vaccine was evaluated in TC-1 tumor model. Results:S-540956 exhibited higher accumulating capacity to lymph nodes in mice compared to a typical CpG adjuvant, ODN2006. Systemic proinflammatory cytokine responses were decreased by combining the complementary strand with amphiphilic chain. S-540956 was efficiently incorporated into plasmacytoid DCs and induced the expression of costimulatory molecules. Cellular immune responses induced by S-540956 adjuvanted peptide vaccine were significantly higher than ODN2006 adjuvanted peptide vaccine. And this enhanced adjuvant effect was observed also in protein vaccine. In TC-1 tumor model, therapeutically administered S-540956 adjuvanted HPV-E7 peptide vaccine lead to significant tumor shrinkage compared to ODN2006 adjuvanted peptide vaccine. Conclusion: S-540956 acted as a potent adjuvant for peptide vaccine by inducing cellular immune responses effectively. Accumulating capacity to lymph nodes of S-540956 is a promising adjuvant for not only for peptide but for protein or other biologic antigens. Citation Format: Takayuki Nakagawa, Motoyasu Onishi, Soichi Tofukuji, Shinya Omoto, Kazufumi Katayama, Akira Kugimiya, Morio N