[ODP6F] f. Immune Mechanism, Development of Vaccines

[ODP-174] Synthetic lipid A of Alcaligenes augments nasal vaccine efficacy to prevent pneumococcal infection

○Ken Yoshii^1,2, Koji Hosomi¹, Atsushi Shimoyama³, Yunru Wang^1,4, Haruki Yamaura³, Takahiro Nagatake¹, Hidehiko Suzuki¹, Huangwenxian Lan^1,4, Hiroshi Kiyono^5,6,7,8, Koichi Fukase³, Jun Kunisawa^{1,2,4,5,9,10,11,12} (¹The Laboratory of Vaccine Materials., NIBIOHN., ²Grad. Sch. Med., Osaka Univ., ³Grad Sch. Sci., Osaka Univ., ⁴Grad Sch. Pharmaceutical Sci., Osaka Univ., ⁵International Research and Development Center for Mucosal Vaccines, IMSUT., ⁶Dept. Mucosal Immunol., IMSUT Distinguished Professor Unit., IMSUT., ⁷Dept. Gastroenterology., Sch. Med and CU-UCSD Center for Mucosal Immunology, Allergy and Vaccine., Univ. California., ⁸Grad Sch. Med., Chiba Univ., ⁹Grad Sch. Dent., Osaka Univ., ¹⁰Grad Sch. Med., Kobe Univ., ¹¹Grad Sch. Biomedical and Health Sci., Hiroshima Univ., ¹²Research Organization for Nano & Life Innovation., Waseda Univ.)

Potent and safe vaccine adjuvants are required to appropriately augment mucosal vaccine effects. Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer's patch resident Alcaligenes suitably stimulated dendritic cells to promote the production of IL-6 and BAFF, thus enhancing antigen-specific immune responses including IgA production and Th17 responses without excessive inflammation. Here, we examined the efficacy of chemically synthesized Alcaligenes lipid A, the biologically active part of LPS, as a nasal vaccine adjuvant. Mice were nasally immunized with pneumococcal surface protein A (PspA) as a vaccine antigen for S. pneumoniae, together with Alcaligenes lipid A. Alcaligenes lipid A induced high levels of PspA-specific nasal IgA and serum IgG production through the induction of germinal center formation in the nasopharynx-associated lymphoid tissue and cervical lymph nodes (CLNs). Moreover, Alcaligenes lipid A promoted PspA-specific Th17 responses in the CLNs and spleen, consequently recruiting neutrophils upon respiratory infection. These immune responses collectively resulted in the protection against S. pneumoniae infection. Taken together, Alcaligenes lipid A could be applied to the prospective adjuvant to enhance nasal vaccine efficacy by activating both the innate and acquired arms of mucosal immunity against respiratory bacterial infection.