The coronavirus disease 2019 (COVID-19) pandemic, caused by the 31SARS‐CoV‐2head region reactive AbSARS‐CoV‐2core regionreactive AbSARS‐CoV‐2Spike RBDSARS‐CoVWIV1‐CoVSpike RBDSpike RBD××Head regionCore region(Conserved Wild typeSARS‐CoV‐2 Spike RBDHead regionCore regionImmunizationGlycan engineeredSARS‐CoV‐2 Spike RBDN‐Glycanregion)β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health crisis. In this year, we carried out three major studies: 1) In order to obtain future effective therapeutic antibodies, we identified the antibody repertoire for SARS-CoV-2 viruses that was generated in infected in-dividuals; 2) In order to make broadly protective vaccines against SARS-related coronaviruses, we designed new types of vaccines and tested whether they work in a mouse model system; 3) In addition, we applied our new type of adjuvant for use in COVID-19 vaccines by expanding our work on influenza vaccine development. This new adjuvant is designed for use in a patch vaccine in the future.SARS-related coronaviruses may cause future outbreaks, therefore broadly protective vaccines are urgently needed. When looking carefully at the structure of the receptor-binding region (RBD) of the spike protein of the SARS-CoV-2 virus, we see that it is composed of the head and the core sub-region, which is directly involved in the entry of SARS-CoV-2 and contributes to the overall structural stability of the RBD region, respectively. Given that the core sub-do-main is structurally well conserved among SARS-related viruses, we intended to make new types of vaccines to elicit neutralizing antibodies against the core sub-domain. For this purpose, we introduced N-linked glycans onto the SARS-CoV-2 RBD surfaces and used them as immunogens in a mouse model. These types of vaccines indeed elicited significant neutralizing activity for not only SARS-CoV-2 but also SARS-related viruses such as bat WIV1-CoV. Apart from antigens, adjuvants are also very important for efficient humoral responses. As mentioned above, we had already developed a new type of adjuvant that facili-tates the Tfh-B cell axis, thereby inducing high-quality and quantity antibodies. Combining this novel type of adjuvant with glycan-engineered antigens for SARS-related viruses, we are attempting to add this new adjuvant for maximiz-ing the production of broadly neutralizing antibodies.Figure: How to construct protective vaccines against not only SARS-CoV-2 but also SARS-CoV and WIV1-CoV virusesIn order to induce antibodies predominantly against re-gions that are structurally conserved in the RBD among SARS-related viruses, glycan engineering was performed to mask the dominant epitope on the RBD head region, which is a structurally non-conserved region. When mice are immunized with this modified RBD vaccine, as expected, antibodies are predominantly induced that recognize the structurally conserved core-RBD region of not only SARS-CoV-2 but also other related SARS-related viruses such as SARS-CoV and WIV1-CoV and were also highly protective against these SARS-related viruses.Recent Major PublicationsShinnakasu R, Sakakibara S, Yamamoto H, Wang PH, Moriyama S, Sax N, Ono C, Yamanaka A, Adachi Y, Onodera T, Sato T, Shinkai M, Suzuki R, Matsuura Y, Hashii N, Takahashi Y, Inoue T, Yamashita K, Kurosaki T. Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses. J Exp Med 218, e20211003 (2021)Inoue T, Shinnakasu R, Kawai C, Ise W, Kawakami E, Sax N, Oki T, Kitamura T, Yamashita K, Fukuyama H, Kuro-saki T. Exit from germinal center to become quiescent memory B cells depends on metabolic reprograming and provision of a survival signal. J Exp Med 218, e20200866. (2021)Fukuyama H, Shinnakasu R, Kurosaki T. Influenza vac-cination strategies targeting the hemagglutinin stem region. Immunol Rev 296, 132-141 (2020)Invited presentationsKurosaki T. “Strategy of Vaccine Development for Variant Viruses” Biopharma EXPO 2021 (Chiba, Japan) December 2021Kurosaki T. “Function of memory B cells and their gen-eration mechanism” FIMSA 2021, 8th FIMSA Congress (Busan, Korea/Online) October 2021Kurosaki T. “When designing dream vaccines, consider the memory B cell behavior” Seminar at Okinawa In-stitute of Science and Technology Graduate University (Okinawa, Japan) April 2021Kurosaki T. “Immune regulation through B lymphocytes” Seminar at Osaka University (Suita, Japan) March 2021Laboratory for Lymphocyte DifferentiationTeam Leader: Tomohiro Kurosaki
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