Additive effects of booster mRNA vaccination and SARS-CoV-2 Omicron infection on T cell immunity across immunocompromised states.

Autor:	Müller TR; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Sekine T; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Trubach D; Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark., Niessl J; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Chen P; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Bergman P; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Department of Laboratory Medicine, Clinical Immunology, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden., Blennow O; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Department of Transplantation, Karolinska University Hospital, Stockholm, Sweden.; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden., Hansson L; Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Mielke S; Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska Comprehensive Cancer Center, Karolinska University Hospital Huddinge, Stockholm, Sweden., Nowak P; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden.; Laboratory for Molecular Infection Medicine Sweden MIMS, Umeå University, Umeå, Sweden., Vesterbacka J; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden., Akber M; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Olofsson A; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Amaya Hernandez SP; Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark., Gao Y; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Cai C; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Söderdahl G; Department of Transplantation, Karolinska University Hospital, Stockholm, Sweden.; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden., Smith CIE; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska Comprehensive Cancer Center, Karolinska University Hospital Huddinge, Stockholm, Sweden., Österborg A; Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Loré K; Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Sällberg Chen M; Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden., Ljungman P; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska Comprehensive Cancer Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.; Department of Medicine Huddinge, Hematology, Karolinska Institutet, Stockholm, Sweden., Ljunggren HG; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden., Karlsson AC; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.; Karolinska University Laboratory, Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden., Saini SK; Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark., Aleman S; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden., Buggert M; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2023 Jul 12; Vol. 15 (704), pp. eadg9452. Date of Electronic Publication: 2023 Jul 12.
DOI:	10.1126/scitranslmed.adg9452
Abstrakt:	Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging SARS-CoV-2 subvariants, it is necessary to assess whether other components of adaptive immunity generate resilient and protective responses against infection. We assessed T cell responses in 279 individuals, covering five different immunodeficiencies and healthy controls, before and after booster mRNA vaccination, as well as after Omicron infection in a subset of patients. We observed robust and persistent Omicron-reactive T cell responses that increased markedly upon booster vaccination and correlated directly with antibody titers across all patient groups. Poor vaccination responsiveness in immunocompromised or elderly individuals was effectively counteracted by the administration of additional vaccine doses. Functionally, Omicron-reactive T cell responses exhibited a pronounced cytotoxic profile and signs of longevity, characterized by CD45RA + effector memory subpopulations with stem cell-like properties and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals appeared protected against severe disease and exhibited enhanced and diversified T cell responses against conserved and Omicron-specific epitopes. Our findings indicate that T cells retain the ability to generate highly functional responses against newly emerging variants, even after repeated antigen exposure and a robust immunological imprint from ancestral SARS-CoV-2 mRNA vaccination.
Databáze:	MEDLINE
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