[WS1] Bacteriological and immunological research that provide an opportunity to advance vaccine development

[WS1-1] Virus-like particle structure enhances protective IgA antibody responses against noroviruses

○Taishi Onodera¹, Kana Hashi¹, Reiko Todaka^2,5, Manabu Ato³, Hideki Hasegawa⁴, Kelsoe Garnet⁵, Kazuhiko Katayama², Yoshimasa Takahashi¹ (¹Dept. Immunol. National Institute of Infectious Deseases, ²Dept. Infection Controland Immunology, Kitasato Univ., ³Dept. Microbial Infection and Immunity. National Institute of Infectious Deseases, ⁴Dept. Influenza Research center. National Institute of Infectious Deseases, ⁵Dept. Immunol. and Human Vaccine Institute, Duke Univ.)

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.