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      T‐cell responses to SARS‐CoV‐2 Omicron spike epitopes with mutations after the third booster dose of an inactivated vaccine

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          Abstract

          The rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant contains more than 30 mutations that mediate escape from antibody responses elicited by prior infection or current vaccines. Fortunately, T‐cell responses are highly conserved in most individuals, but the impacts of mutations are not clear. Here, we showed that the T‐cell responses of individuals who underwent booster vaccination with CoronaVac were largely protective against the SARS‐CoV‐2 Omicron spike protein. To specifically estimate the impact of Omicron mutations on vaccinated participants, 16 peptides derived from the spike protein of the ancestral virus or Omicron strain with mutations were used to stimulate peripheral blood mononuclear cells (PBMCs) from the volunteers. Compared with the administration of two doses of vaccine, booster vaccination substantially enhanced T‐cell activation in response to both the ancestral and Omicron epitopes, although the enhancement was slightly weakened by the Omicron mutations. Then, the peptides derived from these spike proteins were used separately to stimulate PBMCs. Interestingly, compared with the ancestral peptides, only the peptides with the G339D or N440K mutation were detected to significantly destabilize the T‐cell response. Although more participants need to be evaluated to confirm this conclusion, our study nonetheless estimates the impacts of mutations on T‐cell responses to the SARS‐CoV‐2 Omicron variant.

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          Most cited references33

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          Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

          Summary SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We here systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
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            Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

            Preexisting immune response to SARS-CoV-2 Robust T cell responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus occur in most individuals with coronavirus disease 2019 (COVID-19). Several studies have reported that some people who have not been exposed to SARS-CoV-2 have preexisting reactivity to SARS-CoV-2 sequences. The immunological mechanisms underlying this preexisting reactivity are not clear, but previous exposure to widely circulating common cold coronaviruses might be involved. Mateus et al. found that the preexisting reactivity against SARS-CoV-2 comes from memory T cells and that cross-reactive T cells can specifically recognize a SARS-CoV-2 epitope as well as the homologous epitope from a common cold coronavirus. These findings underline the importance of determining the impacts of preexisting immune memory in COVID-19 disease severity. Science, this issue p. 89
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              Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic

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                Author and article information

                Contributors
                didiaodexiaohuo@163.com
                binsu@ccmu.edu.cn
                Journal
                J Med Virol
                J Med Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                06 May 2022
                06 May 2022
                Affiliations
                [ 1 ] Biomedical Pioneering Innovation Center (BIOPIC) Peking University Beijing China
                [ 2 ] Beijing Advanced Innovation Center for Genomics (ICG) Peking University Beijing China
                [ 3 ] Peking‐Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies Peking University Beijing China
                [ 4 ] Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital Capital Medical University Beijing China
                Author notes
                [*] [* ] Correspondence

                Yongzheng Li, Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics (ICG), Peking‐Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.

                Email: didiaodexiaohuo@ 123456163.com

                Bin Su, Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.

                Email: binsu@ 123456ccmu.edu.cn

                [1]

                Yongzheng Li, Xiuwen Wang, and Junyan Jin contributed equally to this study.

                Article
                JMV27814
                10.1002/jmv.27814
                9088599
                35474581
                fc06925f-3e34-4138-9950-0c906527b406
                © 2022 Wiley Periodicals LLC.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                Page count
                Figures: 2, Tables: 0, Pages: 7, Words: 4564
                Product
                Funding
                Funded by: Ministry of Science and Technology of China
                Award ID: CPL‐1233
                Funded by: The National Natural Science Foundation of China (NSFC)
                Award ID: 81772165
                Award ID: 81974303
                Funded by: The High‐Level Public Health Specialized Talents Project of Beijing Municipal Health Commission
                Award ID: 2022‐2‐018
                Funded by: The China Primary Health Care Foundation‐Youan Medical Development Fund
                Award ID: BJYAYY‐2020PY‐01
                Funded by: The "Climbing the peak (Dengfeng)" Talent Training Program of Beijing Hospitals Authority
                Award ID: DFL20191701
                Funded by: The Beijing Health Technologies Promotion Program
                Award ID: BHTPP2020
                Funded by: Beijing Key Laboratory for HIV/AIDS Research
                Award ID: BZ0089
                Funded by: Postdoctoral Fellowship of Peking‐Tsinghua Center for Life Sciences to Y.L.
                Categories
                Short Communication
                Short Communications
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.5 mode:remove_FC converted:10.05.2022

                Microbiology & Virology
                mutations,omicron,sars‐cov‐2,t‐cell responses,vaccine
                Microbiology & Virology
                mutations, omicron, sars‐cov‐2, t‐cell responses, vaccine

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