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Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination.
Gao, Yu; Cai, Curtis; Wullimann, David; Niessl, Julia; Rivera-Ballesteros, Olga; Chen, Puran; Lange, Joshua; Cuapio, Angelica; Blennow, Ola; Hansson, Lotta; Mielke, Stephan; Nowak, Piotr; Vesterbacka, Jan; Akber, Mira; Perez-Potti, Andre; Sekine, Takuya; Müller, Thomas R; Boulouis, Caroline; Kammann, Tobias; Parrot, Tiphaine; Muvva, Jagadeeswara Rao; Sobkowiak, Michal; Healy, Katie; Bogdanovic, Gordana; Muschiol, Sandra; Söderdahl, Gunnar; Österborg, Anders; Hellgren, Fredrika; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Loré, Karin; Sällberg Chen, Margaret; Ljungman, Per; Sandberg, Johan K; Smith, C I Edvard; Bergman, Peter; Ljunggren, Hans-Gustaf; Aleman, Soo; Buggert, Marcus.
  • 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.
  • Wullimann D; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Niessl J; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Rivera-Ballesteros O; 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.
  • Lange J; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Cuapio A; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Blennow O; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Transplantation, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, 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 University Hospital Huddinge, Stockholm, Sweden.
  • Nowak P; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institute, 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 Institute, Stockholm, Sweden.
  • Akber M; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Perez-Potti A; 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.
  • Müller TR; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Boulouis C; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Kammann T; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Parrot T; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Muvva JR; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Sobkowiak M; Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Healy K; Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Bogdanovic G; Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
  • Muschiol S; Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology, 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.
  • Österborg A; Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
  • Hellgren F; Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Grifoni A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Weiskopf D; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Sette A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
  • 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 University Hospital Huddinge, Stockholm, Sweden; Department of Medicine Huddinge, Hematology, Karolinska Institutet, Stockholm, Sweden.
  • Sandberg JK; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Smith CIE; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Bergman P; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.
  • Ljunggren HG; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Aleman S; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institute, Stockholm, Sweden.
  • Buggert M; Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: marcus.buggert@ki.se.
Immunity ; 55(9): 1732-1746.e5, 2022 09 13.
Article in English | MEDLINE | ID: covidwho-2015472
ABSTRACT
Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies Topics: Vaccines Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: J.immuni.2022.07.005

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies Topics: Vaccines Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: J.immuni.2022.07.005