68Table: COVID-19-related research conducted at IMSCoV-2 has continued as a pandemic. The sudden emergence and spread of SARS-CoV-2 poses a threat to global health and the economy. Although current COVID-19 vaccines have shown ef-ficacy in many countries, the development of strategies to prevent the spread of the virus is still needed. At present, several groups in IMS develop tools for COVID-19 diagnosis, others work on the development of prevention and therapeutic strategies. For diagnostics and biomarkers, Momozawa’s group, in collaboration with Tokyo Medical and Dental University, Hiroshima University, and their affiliated hospitals, finished whole-genome sequenc-ing and target sequencing to identify genetic loci associated with individual differences in COVID-19 disease severity. They started to examine the associated genes already reported and perform association analysis to identify new genetic loci. They also depos-ited our whole-genome sequencing data in a global consortium called the COVID Human Genetic Effort. For COVID-19 treat-ment, many groups are working on Cov-2 projects. Among them, several groups are collaborating with RIKEN Drug Discovery and Medical Platforms (DMP). T follicular helper (TFH) cells in the germinal center are helper T cells supporting the production of high-affinity antibodies by B cells. Miyauchi’s group previously reported that both TFH and the IL-4 cytokine derived from TFH cells have an important role for induction of broad-spectrum virus-neutralizing antibodies during influenza virus infection. So far, they have succeeded in generating antibodies that recognize multiple mutant CoV-2 strains by immunizing TFH-activated mice with CoV-2 antigens. Saito’s group is working on the estab-lishment of neutralizing antibodies that target TMPRESS2 instead of the viral spike protein. TMPRESS2 is a host cell membrane protease critical for SARS-CoV-2 viral entry into human cells. Indeed, they established TMPRSS2 mAbs and verified that these mAbs inhibit the infection of human cells by any type of SARS-CoV2 variant. Fukuyama’s group already isolated several thera-peutic human mAbs from COVID-19 patients in collaboration with Keio University. They have patented these antibodies, which are capable of neutralizing several variants of concern (VOC) strains of SARS-CoV-2. Fujii’s group has recently identified a promising QYI peptide for CTL induction against SARS-CoV-2. Since they had previously established the concept of the artificial adjuvant vector cell (aAVC) system against cancer, they estab-lished SARS-CoV-2-derived antigen-expressing aAVC (aAVC-Cov-2). In preclinical studies they obtained evidence for anti-viral cytotoxic T cell induction as well as anti-SARS-CoV-2 Ab in vac-cinated animals. Recent advances as IMS projects in the fields of diagnostics, treatment and vaccine development for SARS-CoV-2 infection are summarized in Table.TeamsHidehiro Fukuyama (Lab. for Lymphocyte Differentiation)Kazuhiko Yamamoto(Laboratory for Autoimmune Diseases)Yasushi Okazaki (Lab. for Comprehensive Genomic Analysis)Yukihide Momozawa(Lab for Genotyping Development)Hidehiro Fukuyama (Lab. For Lymphocyte Differentiation)Kosuke Miyauchi(Lab. for Cytokine Regulation)Kazuyo Moro(Lab. for Innate Immune Systems)Kenya Honda(Lab. for Gut Homeostasis)Hiroshi Ohno(Lab. for Intestinal Ecosystem)Kengo Usui(Genetic Diagnosis Technology Unit)Takashi Saito(Lab. for Cell Signaling)Shin-Ichiro Fujii(Lab. for Immunotherapy)Chikashi Terao(Lab. for Statistical and Translational Genetics)Fumihiko Ishikawa(Lab. for Human Disease Models)Shin-Ichiro Fujii(Lab. for Immunotherapy)TitlesDevelopment of COVID-19 antibody drugDevelopment of a method for healthy immune profiling of people recovering from SARS-CoV-2 infectionGenome analysis of SARS-CoV-2Genome analysis to identify genes and genome loci associated with individual differences in susceptibility to COVID-19 infectionIsolation of new coronavirus detection antibody and development of on-site rapid virus detection kitConstruction of a system to isolate a human monoclonal neutralizing antibody against SARS-CoV-2. (with DMP)Development of a new treatment for severe cases of COVID-19Understanding host-gut microbiota interactions to develop a therapeutic/preventive strategy toward SARS-CoV-2 infectionScreening of drug candidate compounds for COVID-19 in large databases using scalable similarity searchesDevelopment of diagnostic methods using SmartAmp technology (with PMI)Development of monoclonal Ab for TMPRSS (with DMP)Development of aAVC-CoV-2 (with DMP)Elucidating the relationship between somatic cell mosaicism and the risk of COVID-19 infectionMechanism of COVID-19 Severity Caused by Mutant Viruses in the Post-Vaccination PeriodIdentification of cross-reactive epitopes of SARS-CoV-2 to seasonal coronavirusesCOVID-19 projects in IMSCoronavirus disease 2019 (COVID-19) caused by SARS-
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