[ODP6F] f. 免疫機構・ワクチン開発

[ODP-174] 腸管関連リンパ組織内共生菌アルカリゲネスの菌体成分リピドAを用いた経鼻ワクチンアジュバントへの応用

○吉井 健^1,2，細見 晃司¹，下山 敦史³，王 韻茹^1,4，山浦 遼生³，長竹 貴広¹，鈴木 英彦¹，藍 黄文顕^1,4，清野 宏^5,6,7,8，深瀬 浩一³，國澤 純^{1,2,4,5,9,10,11,12} (¹医薬健栄研・ワクチンマテリアルプロジェクト，²阪大・院医，³阪大・院理，⁴阪大・院薬，⁵東大医科研・国際粘膜ワクチン開発研究センター，⁶東大医科研・東大特任教授部門・粘膜免疫学部門，⁷カルフォルニア大サンディエゴ校（UCSD）医学部　千葉大学―UCSD粘膜免疫，アレルギー，ワクチン研究センター，⁸千葉大・院医，⁹阪大・院歯，¹⁰神大・院医，¹¹広大・院医歯薬保健，¹²早稲田大・ナノ・ライフ創新研究機構)

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.