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      Immune response and protective efficacy of the SARS-CoV-2 recombinant spike protein vaccine S-268019-b in mice

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          Abstract

          Vaccines that efficiently target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease (COVID-19), are the best means for controlling viral spread. This study evaluated the efficacy of the COVID-19 vaccine S-268019-b, which comprises the recombinant full-length SARS-CoV-2 spike protein S-910823 (antigen) and A-910823 (adjuvant). In addition to eliciting both Th1-type and Th2-type cellular immune responses, two doses of S-910823 plus A-910823 induced anti-spike protein IgG antibodies and neutralizing antibodies against SARS-CoV-2. In a SARS-CoV-2 challenge test, S-910823 plus A-910823 mitigated SARS-CoV-2 infection-induced weight loss and death and inhibited viral replication in mouse lungs. S-910823 plus A-910823 promoted cytokine and chemokine at the injection site and immune cell accumulation in the draining lymph nodes. This led to the formation of germinal centers and the induction of memory B cells, antibody-secreting cells, and memory T cells. These findings provide fundamental property of S-268019-b, especially importance of A-910823 to elicit humoral and cellular immune responses.

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          Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

          Journal of Clinical Investigation
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            Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

            Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.
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              Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells

              A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many countries globally. Here, we show that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.
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                Author and article information

                Contributors
                shinya.oomoto@shionogi.co.jp
                hasegawa@niid.go.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                2 December 2022
                2 December 2022
                2022
                : 12
                : 20861
                Affiliations
                [1 ]GRID grid.419164.f, ISNI 0000 0001 0665 2737, Laboratory for Bio-Drug Discovery, , Shionogi & Co., Ltd., ; 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825 Japan
                [2 ]GRID grid.410795.e, ISNI 0000 0001 2220 1880, Department of Pathology, , National Institute of Infectious Diseases, ; 4-7-1, Gakuen, Musashimurayama-shi, Tokyo 208-0011 Japan
                [3 ]GRID grid.419164.f, ISNI 0000 0001 0665 2737, Laboratory for Bio-Modality Research, , Shionogi & Co., Ltd., ; 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825 Japan
                [4 ]UMN Pharma Inc., 7F, Tekko Building, 1-8-2, Marunouchi, Chiyoda-ku, Tokyo 100-0005 Japan
                [5 ]GRID grid.419164.f, ISNI 0000 0001 0665 2737, Laboratory for Drug Discovery and Disease Research, , Shionogi & Co., Ltd., ; 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825 Japan
                [6 ]GRID grid.419164.f, ISNI 0000 0001 0665 2737, Medical Science Department, , Shionogi & Co., Ltd., ; 8F, Nissei East Building, 3-3-16, Imabashi, Chuo-ku, Osaka 541-0032 Japan
                [7 ]GRID grid.258799.8, ISNI 0000 0004 0372 2033, Laboratory of Medical Virology, Institute for Life and Medical Sciences, , Kyoto University, ; 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 Japan
                [8 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Department of Virology, Faculty of Medicine, , Kyushu University, ; 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 Japan
                [9 ]GRID grid.410795.e, ISNI 0000 0001 2220 1880, Department of Pathology, , National Institute of Infectious Diseases, ; 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640 Japan
                [10 ]GRID grid.410795.e, ISNI 0000 0001 2220 1880, Center for Influenza and Respiratory Virus Research, , National Institute of Infectious Diseases, ; 4-7-1, Gakuen, Musashimurayama-shi, Tokyo 208-0011 Japan
                Article
                25418
                10.1038/s41598-022-25418-5
                9718471
                36460696
                6695f043-d849-4317-a6e1-851e89ab13cd
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 July 2022
                : 29 November 2022
                Funding
                Funded by: Shionogi & Co., Ltd.
                Funded by: FundRef http://dx.doi.org/10.13039/100009619, Japan Agency for Medical Research and Development;
                Award ID: JP21nf0101626
                Award ID: JP21nf0101626
                Award ID: JP21nf0101626
                Award ID: JP21nf0101626
                Award Recipient :
                Categories
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                © The Author(s) 2022

                Uncategorized
                immunology,medical research
                Uncategorized
                immunology, medical research

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