[WS1] ワクチン開発を進めるきっかけとなった細菌学・免疫学研究

[WS1-1] ウイルス様粒子構造はノロウイルスに対するIgA抗体応答を増強する

○小野寺 大志¹，橋 香奈¹，戸高 玲子^2,5，阿戸 学³，長谷川 秀樹⁴，Kelsoe Garnet⁵，片山 和彦²，高橋 宜聖¹ (¹国立感染症研究所・免疫部，²北里大・ウイルス感染制御学，³国立感染症研究所・感染制御部，⁴国立感染症研究所・インフルエンザ研究センター，⁵デューク大学・免疫学ヒトワクチン研究所)

Noroviruses (NoVs) are the leading cause of acute epidemic gastroenteritis in worldwide. Because of the extensive damages in health and economics, development of effective vaccines is strongly desired. Virus-like particles (VLPs) which are self-assembled of recombinantly expressed norovirus VP1 protein are made as first generation of vaccine candidate against norovirus. Since noroviruses are known to infect through mucosal surface, induction of IgA Abs by vaccination is thought to be beneficial to provide more effective immunity. In this study, we evaluated the effectiveness of norovirus GI.1- and GII.4-VLP vaccines for human immunity by utilizing a humanized mouse model. This mouse model successfully demonstrates human IgG and IgA class of protective Ab responses after the NoV-VLP vaccination. Notably, although equivalent numbers of IgG and IgA memory B cells specific for each VLP are present in donor PBMCs, IgA Ab responses are markedly enhanced compared with IgG after the vaccination with VLP but not with disrupted VLP which lacks self-assembled VP1 structure, indicating that the highly organized structure of VLP is crucial for IgA enhancement. Thus, our results demonstrate that the highly organized structure of norovirus VLP is an important factor to enhance protective IgA Ab production against noroviruses.