樹状細胞を活性化する経鼻DNAアジュバントの開発 : 感染症・NCD制御を目指す粘膜ワクチン

WHO（2014）のレポートでは, 2012年全世界の総死亡数は5,600万人であり，その内訳として非感染性疾患（NCD）によるものが約3,600万人＊1，感染症が約950万人と報告している＊2．超高齢社会のわが国においても，悪性新生物（ガン），心疾患，肺炎による死亡数は上位を占め，年々増加の一途をたどっており，「健康寿命の延伸」と「健康格差の縮小」はわが国の保健政策の課題となっている．
われわれはこれまで，粘膜からの病原微生物の侵入阻止ならびに侵入後の体内防御を可能とする粘膜ワクチンの研究を行ってきた．本稿では，粘膜ワクチンによって誘導される粘膜免疫応答と経鼻投与型（経鼻）ワクチンの特性について述べたうえで，樹状細胞を活性化するサイトカインFlt3 ligandを発現するDNAベクターや，CpGオリゴデオキシヌクレオチドを併用した粘膜DNAアジュバント（免疫賦活化剤）について，われわれのこれまでの研究開発について概説する．またそれらアジュバントを用いた経鼻ワクチンが，肺炎球菌感染下の老齢マウスにおいて，若齢マウスとかわらない免疫応答を誘導し肺炎球菌の定着を阻害することや，歯周病原細菌感染により誘発したアテローム性動脈硬化を経鼻ワクチンが抑制することを紹介する．
近い将来，粘膜ワクチンが，感染症だけでなくNCDをも制御し，わが国の「健康寿命の延伸」と「健康格差の縮小」という国家課題の克服と，世界的に進行する高齢社会の人々のQOL向上に貢献するツールになりうることを期待する．

According to reports from the World Health Organization in 2014, non-communicable diseases (NCDs) are responsible for the deaths of more than 36 million people (~63% of the global total) annually, while infectious diseases are responsible for another 9.5 million (about 20% of the global total). Similar rates are seen in Japan, which has a super-aging society with increasing mortality due to cancer, ischemic heart disease, and pneumonia. Japan is also faced with national issues such as “the extension of healthy life expectancy” and “the reduction of health disparities”, which are the ultimate objectives to be realized through improvements in the lifestyle and social environment. Health care policies and approaches have therefore tended to shift in focus from society to the individual.
To date, we have investigated some novel nasal adjuvants for the improvement of mucosal vaccine that could induce a mucosal immune system in order to prevent invasion by infectious agents and environmental antigens through the mucosal surfaces. In this review, we briefly summarize our findings regarding the development and verification of novel nasal DNA adjuvants to target the activation of nasopharyngeal-associated lymphoid tissue (NALT) dendritic cells for use as nasal vaccines.
In addition, we examined whether nasal vaccines using our newly developed nasal DNA adjuvants are effective at preventing pneumococcal infection in elderly as well as young mice, and whether nasal immunization with Porphyromonas gingivalis (P. gingivalis) outer membrane protein and cholera toxin as an adjuvant prevents atherosclerosis induced by P. gingivalis infection.
We hope that the results of this study will promote the development of mucosal vaccine including nasal vaccines capable of controlling NCDs as well as infectious diseases in the near future, which will promote successful outcomes to help improve the quality of life of human beings in a super-aging society.