The Infectious Diseases Research Unit was established in response to the 37demand for a BSL-3 and ABSL-3 facility during the 2021 (COVID-19) pandemic. Since then, the unit has played a central role in RIKEN’s research on the immune response to SARS-CoV-2 and the development of novel therapies and new vaccines against COVID-19.One of our primary missions is to support research on infectious diseases inside and outside the Center. For this mission, the unit operates the BSL-3 facility and the ABSL-3 for virus research using cell culture systems and small animal models, respectively. We have collaborated with more than four intra-IMS teams and more than three institutions outside RIKEN.Our unit focuses on the elucidation of the mechanism of neutralizing anti-body production against SARS-CoV-2 and the development of a new vaccine. Using the BSL-3 facility, we have identified human broadly neutralizing mono-clonal antibodies from convalescent COVID-19 patients (Figure 1). In addition, we have developed novel vaccine-strategies and therapies as collaborations with other IMS groups.The research unit has established a novel SARS-CoV-2 susceptible mouse model, a human ACE2 knock-in mouse based on a C57BL/6 background, which can be easily crossed with other genetically modified mice such as im-munocompromised mice. Other CoV-2 mouse models are also available and are used to study pathogenesis in severe conditions. Using these models, we are conducting research on SARS-CoV-2-specific CTLs and on factors that exacerbate the pathogenesis of CoV-2 infection, in collaboration with external research institutions outside RIKEN. To prepare for new viral pandemics of concern in the future, we aim to deepen our knowledge of viral infections and immune responses to help provide rapid and appropriate therapies and vac-cines.Figure: Broadly neutralizing antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescent patientsDuring the CoV-2 pandemics, collaborating with the KEIO University, we isolated a series of human neutraliz-ing antibodies against CoV-2. At the top is a flow cytom-etry profile showing binding of memory B cells to both Wuhan- and Gamma-RBDs. The neutralization breadth of antibodies cloned from these cells was tested in the RIKEN BSL-3 using several VOCs. The Cryo-electron mi-croscope structure study defined the epitopes of those antibodies, which block the Spike-ACE2 interactions.iScience 26, 106955 (2023)Recent Major PublicationsTakeshita M, Fukuyama Y, Kamada K, Matsumoto T, Makino-Okamura C, Lin Q, Sakuma M, Kawahara E, Yamazaki I, Uchikubo-Kamo T, Tomabechi Y, Hanada K, Hisano T, Moriyama S, Takahashi Y, Ito M, Imai M, Mae-mura T, Furusawa Y, Yamayoshi S, Kawaoka Y, Shirouzu M, Ishi M, Saya H, Kondo Y, Kaneko Y, Suzuki K, Fukunaga K, Takeuchi T, Keio Donner Project. Potent neutralizing broad-spectrum antibody against SARS-CoV-2 gener-ated from dual-antigen-specific B cells from convales-cents. iScience 26, 106955 (2023)Nihei Y, Higashiyama M, Miyauchi K, Haniuda K, Suzuki Y, Kubo M, Kitamura D. Subcutaneus immunization with zymosan generates mucosal igA-eliciting memory and protects mice from heterologous influenza virus infec-tion. Int Immunol 35, 277-386 (2023)Takeshita M, Fukuyama H, Kamada K, Matsumoto T, Makino-Okamura C, Uchikubo-Kamo T, Tomabechi Y, Ha-nada K, Moriyama S, Takahashi Y, Ishigaki H, Nakayama M, Nguyen CT, Kitagawa Y, Itoh Y, Imai M, Maemura T, Furusawa Y, Ueki H, Iwatsuki-Horimoto K, Ito M, Yamay-oshi S, Kawaoka Y, Shirouzu M, Ishii M, Saya H, Kondo Y, Kaneko Y, Suzuki K, Fukunaga K, Takeuchi T. SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models. iScience 25, 105596 (2022)Invited presentationsFukuyama H ”The 1st International Electronic Confer-ence on Vaccines: RNA Vaccines, Current Challenges and Future Developments” IECV 2023 (Online) December 2023Infectious Diseases Research UnitUnit Leader: Haruhiko Koseki
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