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1. Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination: a one-year follow-up of the prospective clinical trial COVAXID

Author

Chen, Puran, Bergman, Peter, Blennow, Ola, Hansson, Lotta, Mielke, Stephan, Nowak, Piotr, Söderdahl, Gunnar, Österborg, Anders, Smith, C.I. Edvard, Vesterbacka, Jan, Wullimann, David, Cuapio, Angelica, Akber, Mira, Bogdanovic, Gordana, Muschiol, Sandra, Åberg, Mikael, Loré, Karin, Sällberg Chen, Margaret, Buggert, Marcus, Ljungman, Per, Aleman, Soo, and Ljunggren, Hans-Gustaf

Published
2023
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3. NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals

Author

Cuapio, Angelica, Boulouis, Caroline, Filipovic, Iva, Wullimann, David, Kammann, Tobias, Parrot, Tiphaine, Chen, Puran, Akber, Mira, Gao, Yu, Hammer, Quirin, Strunz, Benedikt, Pérez Potti, André, Rivera Ballesteros, Olga, Lange, Joshua, Muvva, Jagadeeswara Rao, Bergman, Peter, Blennow, Ola, Hansson, Lotta, Mielke, Stephan, Nowak, Piotr, Söderdahl, Gunnar, Österborg, Anders, Smith, C. I. Edvard, Bogdanovic, Gordana, Muschiol, Sandra, Hellgren, Fredrika, Loré, Karin, Sobkowiak, Michal J., Gabarrini, Giorgio, Healy, Katie, Sällberg Chen, Margaret, Alici, Evren, Björkström, Niklas K., Buggert, Marcus, Ljungman, Per, Sandberg, Johan K., Aleman, Soo, and Ljunggren, Hans-Gustaf

Published
2022
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4. MAIT cell compartment characteristics are associated with the immune response magnitude to the BNT162b2 mRNA anti-SARS-CoV-2 vaccine

Author

Boulouis, Caroline, Kammann, Tobias, Cuapio, Angelica, Parrot, Tiphaine, Gao, Yu, Mouchtaridi, Elli, Wullimann, David, Lange, Joshua, Chen, Puran, Akber, Mira, Rivera Ballesteros, Olga, Muvva, Jagadeeswara Rao, Smith, C. I. Edvard, Vesterbacka, Jan, Kieri, Oscar, Nowak, Piotr, Bergman, Peter, Buggert, Marcus, Ljunggren, Hans-Gustaf, Aleman, Soo, and Sandberg, Johan K.

Published
2022
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5. Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Author

Ingelman-Sundberg, Hanna M., Blixt, Lisa, Wullimann, David, Wu, Jinghua, Gao, Yu, Healy, Katie, Muschiol, Sandra, Bogdanovic, Gordana, Åberg, Mikael, Kjellander, Christian, Grifoni, Alba, Sette, Alessandro, Aleman, Soo, Chen, Puran, Blennow, Ola, Hansson, Lotta, Ljunggren, Hans-Gustaf, Sallberg Chen, Margaret, Buggert, Marcus, Österborg, Anders, Ingelman-Sundberg, Hanna M., Blixt, Lisa, Wullimann, David, Wu, Jinghua, Gao, Yu, Healy, Katie, Muschiol, Sandra, Bogdanovic, Gordana, Åberg, Mikael, Kjellander, Christian, Grifoni, Alba, Sette, Alessandro, Aleman, Soo, Chen, Puran, Blennow, Ola, Hansson, Lotta, Ljunggren, Hans-Gustaf, Sallberg Chen, Margaret, Buggert, Marcus, and Österborg, Anders

Published
2024
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6. Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Author

Ingelman-Sundberg, Hanna M., primary, Blixt, Lisa, additional, Wullimann, David, additional, Wu, Jinghua, additional, Gao, Yu, additional, Healy, Katie, additional, Muschiol, Sandra, additional, Bogdanovic, Gordana, additional, Åberg, Mikael, additional, Kjellander, Christian, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, Aleman, Soo, additional, Chen, Puran, additional, Blennow, Ola, additional, Hansson, Lotta, additional, Ljunggren, Hans-Gustaf, additional, Chen, Margaret Sällberg, additional, Buggert, Marcus, additional, and Österborg, Anders, additional

Published
2023
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7. Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia

Author

Andersson, Maria, primary, Wu, Jinghua, additional, Wullimann, David, additional, Gao, Yu, additional, Aberg, Mikael, additional, Muschiol, Sandra, additional, Healy, Katie, additional, Naud, Sabrina, additional, Bogdanovic, Gordana, additional, Palma, Marzia, additional, Mellstedt, Hakan, additional, Chen, Puran, additional, Ljunggren, Hans-Gustaf, additional, Hansson, Lotta, additional, Sallberg Chen, Margaret, additional, Buggert, Marcus, additional, Ingelman-Sundberg, Hanna M., additional, and Osterborg, Anders, additional

Published
2023
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8. Functional SARS-CoV-2 cross-reactive CD4 + T cells established in early childhood decline with age

Author

Humbert, Marion, primary, Olofsson, Anna, additional, Wullimann, David, additional, Niessl, Julia, additional, Hodcroft, Emma B., additional, Cai, Curtis, additional, Gao, Yu, additional, Sohlberg, Ebba, additional, Dyrdak, Robert, additional, Mikaeloff, Flora, additional, Neogi, Ujjwal, additional, Albert, Jan, additional, Malmberg, Karl-Johan, additional, Lund-Johansen, Fridtjof, additional, Aleman, Soo, additional, Björkhem-Bergman, Linda, additional, Jenmalm, Maria C., additional, Ljunggren, Hans-Gustaf, additional, Buggert, Marcus, additional, and Karlsson, Annika C., additional

Published
2023
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9. Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia

Author

Andersson, Maria, Wu, Jinghua, Wullimann, David, Gao, Yu, Åberg, Mikael, Muschiol, Sandra, Healy, Katie, Naud, Sabrina, Bogdanovic, Gordana, Palma, Marzia, Mellstedt, Hakan, Chen, Puran, Ljunggren, Hans-Gustaf, Hansson, Lotta, Sallberg Chen, Margaret, Buggert, Marcus, Ingelman-Sundberg, Hanna M., Osterborg, Anders, Andersson, Maria, Wu, Jinghua, Wullimann, David, Gao, Yu, Åberg, Mikael, Muschiol, Sandra, Healy, Katie, Naud, Sabrina, Bogdanovic, Gordana, Palma, Marzia, Mellstedt, Hakan, Chen, Puran, Ljunggren, Hans-Gustaf, Hansson, Lotta, Sallberg Chen, Margaret, Buggert, Marcus, Ingelman-Sundberg, Hanna M., and Osterborg, Anders

Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination. Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides. Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors. Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Syste, In the publication, Mikael Åberg i misspelled as Mikael Aberg

Published
2023
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10. Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Author

Ingelman-Sundberg, Hanna, primary, Blixt, Lisa, additional, Wullimann, David, additional, Wu, Jinghua, additional, Gao, Yu, additional, Healy, Katie, additional, Muschiol, Sandra, additional, Bogdanovic, Gordana, additional, Åberg, Mikael, additional, Kjellander, Christian, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, Aleman, Soo, additional, Chen, Puran, additional, Blennow, Ola, additional, Hansson, Lotta, additional, Ljunggren, Hans-Gustaf, additional, Chen, Margaret Sällberg, additional, Buggert, Marcus, additional, and Österborg, Anders, additional

Published
2023
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11. Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination

Author

Blixt, Lisa, primary, Gao, Yu, additional, Wullimann, David, additional, Murén Ingelman-Sundberg, Hanna, additional, Muschiol, Sandra, additional, Healy, Katie, additional, Bogdanovic, Gordana, additional, Pin, Elisa, additional, Nilsson, Peter, additional, Kjellander, Christian, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, Sällberg Chen, Margaret, additional, Ljunggren, Hans-Gustaf, additional, Buggert, Marcus, additional, Hansson, Lotta, additional, and Österborg, Anders, additional

Published
2022
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12. Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination

Author

Gao, Yu, primary, Cai, Curtis, additional, Wullimann, David, additional, Niessl, Julia, additional, Rivera-Ballesteros, Olga, additional, Chen, Puran, additional, Lange, Joshua, additional, Cuapio, Angelica, additional, Blennow, Ola, additional, Hansson, Lotta, additional, Mielke, Stephan, additional, Nowak, Piotr, additional, Vesterbacka, Jan, additional, Akber, Mira, additional, Perez-Potti, Andre, additional, Sekine, Takuya, additional, Müller, Thomas R., additional, Boulouis, Caroline, additional, Kammann, Tobias, additional, Parrot, Tiphaine, additional, Muvva, Jagadeeswara Rao, additional, Sobkowiak, Michal, additional, Healy, Katie, additional, Bogdanovic, Gordana, additional, Muschiol, Sandra, additional, Söderdahl, Gunnar, additional, Österborg, Anders, additional, Hellgren, Fredrika, additional, Grifoni, Alba, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Loré, Karin, additional, Sällberg Chen, Margaret, additional, Ljungman, Per, additional, Sandberg, Johan K., additional, Smith, C.I. Edvard, additional, Bergman, Peter, additional, Ljunggren, Hans-Gustaf, additional, Aleman, Soo, additional, and Buggert, Marcus, additional

Published
2022
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13. Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination

Author

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, 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, and Buggert, Marcus

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.

Published
2022
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14. Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination

Author

Blixt, Lisa, Gao, Yu, Wullimann, David, Ingelman-Sundberg, Hanna Muren, Muschiol, Sandra, Healy, Katie, Bogdanovic, Gordana, Pin, Elisa, Nilsson, Peter, Kjellander, Christian, Grifoni, Alba, Sette, Alessandro, Chen, Margaret Sallberg, Ljunggren, Hans -Gustaf, Buggert, Marcus, Hansson, Lotta, Osterborg, Anders, Blixt, Lisa, Gao, Yu, Wullimann, David, Ingelman-Sundberg, Hanna Muren, Muschiol, Sandra, Healy, Katie, Bogdanovic, Gordana, Pin, Elisa, Nilsson, Peter, Kjellander, Christian, Grifoni, Alba, Sette, Alessandro, Chen, Margaret Sallberg, Ljunggren, Hans -Gustaf, Buggert, Marcus, Hansson, Lotta, and Osterborg, Anders

Abstract

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Published
2022
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15. Additional file 2 of NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals

Author

Cuapio, Angelica, Boulouis, Caroline, Filipovic, Iva, Wullimann, David, Kammann, Tobias, Parrot, Tiphaine, Chen, Puran, Akber, Mira, Gao, Yu, Hammer, Quirin, Strunz, Benedikt, P��rez Potti, Andr��, Rivera Ballesteros, Olga, Lange, Joshua, Muvva, Jagadeeswara Rao, Bergman, Peter, Blennow, Ola, Hansson, Lotta, Mielke, Stephan, Nowak, Piotr, S��derdahl, Gunnar, ��sterborg, Anders, Smith, C. I. Edvard, Bogdanovic, Gordana, Muschiol, Sandra, Hellgren, Fredrika, Lor��, Karin, Sobkowiak, Michal J., Gabarrini, Giorgio, Healy, Katie, S��llberg Chen, Margaret, Alici, Evren, Bj��rkstr��m, Niklas K., Buggert, Marcus, Ljungman, Per, Sandberg, Johan K., Aleman, Soo, and Ljunggren, Hans-Gustaf

Abstract

Additional file 2: Figure S1. Gating strategy for flow cytometry analysis, related to Figs. 1���4. A Gating strategy for phenotypic identification of lymphocytic and monocytic cell populations and subsets by flow cytometry in peripheral blood. B Gating strategy for identification of functional lymphocytic cell populations by flow cytometry in peripheral blood. Figure S2. Lymphocytic and monocytic cell frequencies after BNT162b2 mRNA vaccine administration, related to Fig. 1. A Frequency of lymphocytic (T and B cells and their subsets) and monocytic cell subsets at Days 0, 10, 21 and 35 in the healthy individuals and immunocompromised patients receiving two doses of the BNT162b2 mRNA vaccine according to label. Healthy individuals (Day 0 n = 37, Day 10 n = 38, Day 21 n = 36, Day 35 n = 37), PLWH (Day 0 n = 48, Day 10 n = 46, Day 21 n = 44, Day 35 n = 44), PID (Day 0 n = 12, Day 10 n = 16, Day 21 n = 14, Day 35 n = 12), SOT (Day 0 n = 34, Day 10 n = 33, Day 21 n = 33, Day 35 n = 30). Kruskal���Wallis test followed by a Dunn���s multiple comparisons test. No statistical significance difference was observed within each respective group (i.e., when comparing days 0, 10, 21 and 35).

Published
2022
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16. The Karolinska KI/K COVID-19 immune atlas: An open resource for immunological research and educational purposes

Author

Ljunggren, Hans-Gustaf, Ask, Eivind Heggernes, Cornillet, Martin, Strunz, Benedikt, Chen, Puran, Rao Muvva, Jagadeeswara, Akber, Mira, Buggert, Marcus, Chambers, Benedict J., Cuapio Gomez, Angelica, Dzidic, Majda, Filipovic, Iva, Flodström-Tullberg, Malin, Garcia, Marina, Gorin, Jean-Baptiste, Gredmark-Russ, Sara, Hertwig, Laura, Klingström, Jonas, Kokkinou, Efthymia, Kvedaraite, Egle, Lourda, Magda, Mjösberg, Jenny, Maucourant, Christopher, Norrby-Teglund, Anna, Palma Medina, Laura M., Parrot, Tiphaine, Perez-Potti, André, Ponzetta, Andrea, Ringqvist, Emma, Rivera-Ballesteros, Olga, Rooyackers, Olav, Sandberg, Johan K., Sandberg, John Tyler, Sekine, Takuya, Svensson, Mattias, Varnaite, Renata, Wullimann, David, Eriksson, Lars I., Aleman, Soo, Malmberg, Karl-Johan, Strålin, Kristoffer, and Björkström, Niklas K.

Subjects
Immunology, General Medicine
Abstract

The Karolinska KI/K COVID-19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS-CoV-2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response towards SARS-CoV-2 infection in humans, as it occurred during the first wave. The Immune Atlas was built as an open resource for broad research and educational purposes. It contains a presentation of the response evoked by different immune and inflammatory cells in defined naïve patient-groups as they presented with moderate and severe COVID-19 disease. The present Resource Article describes how the Karolinska KI/K COVID-19 Immune Atlas allows scientists, students, and other interested parties to freely explore the nature of the immune response towards human SARS-CoV-2 infection in an online setting.

Published
2022

17. Additional file 1 of NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals

Author

Cuapio, Angelica, Boulouis, Caroline, Filipovic, Iva, Wullimann, David, Kammann, Tobias, Parrot, Tiphaine, Chen, Puran, Akber, Mira, Gao, Yu, Hammer, Quirin, Strunz, Benedikt, P��rez Potti, Andr��, Rivera Ballesteros, Olga, Lange, Joshua, Muvva, Jagadeeswara Rao, Bergman, Peter, Blennow, Ola, Hansson, Lotta, Mielke, Stephan, Nowak, Piotr, S��derdahl, Gunnar, ��sterborg, Anders, Smith, C. I. Edvard, Bogdanovic, Gordana, Muschiol, Sandra, Hellgren, Fredrika, Lor��, Karin, Sobkowiak, Michal J., Gabarrini, Giorgio, Healy, Katie, S��llberg Chen, Margaret, Alici, Evren, Bj��rkstr��m, Niklas K., Buggert, Marcus, Ljungman, Per, Sandberg, Johan K., Aleman, Soo, and Ljunggren, Hans-Gustaf

Abstract

Additional file 1: Table S1. List of reagents used in the present study. Table S2. Antibodies used for Panel 1. Table S3. Antibodies used for Panel 2.

Published
2022
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18. Additional file 1 of MAIT cell compartment characteristics are associated with the immune response magnitude to the BNT162b2 mRNA anti-SARS-CoV-2 vaccine

Author

Boulouis, Caroline, Kammann, Tobias, Cuapio, Angelica, Parrot, Tiphaine, Gao, Yu, Mouchtaridi, Elli, Wullimann, David, Lange, Joshua, Chen, Puran, Akber, Mira, Rivera Ballesteros, Olga, Muvva, Jagadeeswara Rao, Smith, C. I. Edvard, Vesterbacka, Jan, Kieri, Oscar, Nowak, Piotr, Bergman, Peter, Buggert, Marcus, Ljunggren, Hans-Gustaf, Aleman, Soo, and Sandberg, Johan K.

Abstract

Additional file 1: Figure S1. MAIT cell associations with adaptive immune responses against the BNT162b2 mRNA vaccination in patients with primary and acquired immunodeficiency. Figure S2. MAIT cell phenotypic characteristics unchanged in patients with primary and acquired and immunodeficiency vaccinated with the BNT162b2 mRNA vaccine. Figure S3. No significant changes or associations between the overall non-MAIT T cell compartment and adaptive immune responses to the BNT162b2 mRNA vaccine. Figure S4. Preserved MAIT cell response to IL-12 and IL-18 co-stimulation throughout BNT162b2 mRNA vaccination. Table S1. Flow cytometry antibodies and reagents used in the phenotype panel. Table S2. Flow cytometry antibodies and reagent used in the functional panel. Table S3. Key resource table.

Published
2022
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19. T-cell immune responses following vaccination with mRNA BNT162b2 against SARS-CoV-2 in patients with chronic lymphocytic leukemia: results from a prospective open-label clinical trial

Author

Blixt, Lisa, primary, Wullimann, David, additional, Aleman, Soo, additional, Lundin, Jeanette, additional, Chen, Puran, additional, Gao, Yu, additional, Cuapio, Angelica, additional, Akber, Mira, additional, Lange, Joshua, additional, Rivera-Ballesteros, Olga, additional, Buggert, Marcus, additional, Ljunggren, Hans-Gustaf, additional, Hansson, Lotta, additional, and Österborg, Anders, additional

Published
2022
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20. Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial

Author

Bergman, Peter, primary, Blennow, Ola, additional, Hansson, Lotta, additional, Mielke, Stephan, additional, Nowak, Piotr, additional, Chen, Puran, additional, Söderdahl, Gunnar, additional, Österborg, Anders, additional, Smith, C. I. Edvard, additional, Wullimann, David, additional, Vesterbacka, Jan, additional, Lindgren, Gustaf, additional, Blixt, Lisa, additional, Friman, Gustav, additional, Wahren-Borgström, Emilie, additional, Nordlander, Anna, additional, Gomez, Angelica Cuapio, additional, Akber, Mira, additional, Valentini, Davide, additional, Norlin, Anna-Carin, additional, Thalme, Anders, additional, Bogdanovic, Gordana, additional, Muschiol, Sandra, additional, Nilsson, Peter, additional, Hober, Sophia, additional, Loré, Karin, additional, Chen, Margaret Sällberg, additional, Buggert, Marcus, additional, Ljunggren, Hans-Gustaf, additional, Ljungman, Per, additional, and Aleman, Soo, additional

Published
2021
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21. Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial

Author

Bergman, Peter, Blennow, Ola, Hansson, Lotta, Mielke, Stephan, Nowak, Piotr, Chen, Puran, Söderdahl, Gunnar, Österborg, Anders, Smith, C. I. Edvard, Wullimann, David, Vesterbacka, Jan, Lindgren, Gustaf, Blixt, Lisa, Friman, Gustav, Wahren-Borgström, Emilie, Nordlander, Anna, Gomez, Angelica Cuapio, Akber, Mira, Valentini, Davide, Norlin, Anna-Carin, Thalme, Anders, Bogdanovic, Gordana, Muschiol, Sandra, Nilsson, Peter, Hober, Sophia, Loré, Karin, Chen, Margaret Sällberg, Buggert, Marcus, Ljunggren, Hans-Gustaf, Ljungman, Per, Aleman, Soo, Bergman, Peter, Blennow, Ola, Hansson, Lotta, Mielke, Stephan, Nowak, Piotr, Chen, Puran, Söderdahl, Gunnar, Österborg, Anders, Smith, C. I. Edvard, Wullimann, David, Vesterbacka, Jan, Lindgren, Gustaf, Blixt, Lisa, Friman, Gustav, Wahren-Borgström, Emilie, Nordlander, Anna, Gomez, Angelica Cuapio, Akber, Mira, Valentini, Davide, Norlin, Anna-Carin, Thalme, Anders, Bogdanovic, Gordana, Muschiol, Sandra, Nilsson, Peter, Hober, Sophia, Loré, Karin, Chen, Margaret Sällberg, Buggert, Marcus, Ljunggren, Hans-Gustaf, Ljungman, Per, and Aleman, Soo

Abstract

Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.

Published
2021
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22. Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19

Author

Sekine, Takuya, Perez-Potti, André, Rivera-Ballesteros, Olga, Strålin, Kristoffer, Gorin, Jean Baptiste, Olsson, Annika, Llewellyn-Lacey, Sian, Kamal, Habiba, Bogdanovic, Gordana, Muschiol, Sandra, Wullimann, David J., Kammann, Tobias, Emgård, Johanna, Parrot, Tiphaine, Folkesson, Elin, Rooyackers, Olav, Eriksson, Lars I., Henter, Jan Inge, Sönnerborg, Anders, Allander, Tobias, Albert, Jan, Nielsen, Morten, Klingström, Jonas, Gredmark-Russ, Sara, Björkström, Niklas K., Sandberg, Johan K., Price, David A., Ljunggren, Hans Gustaf, Aleman, Soo, Buggert, Marcus, Sekine, Takuya, Perez-Potti, André, Rivera-Ballesteros, Olga, Strålin, Kristoffer, Gorin, Jean Baptiste, Olsson, Annika, Llewellyn-Lacey, Sian, Kamal, Habiba, Bogdanovic, Gordana, Muschiol, Sandra, Wullimann, David J., Kammann, Tobias, Emgård, Johanna, Parrot, Tiphaine, Folkesson, Elin, Rooyackers, Olav, Eriksson, Lars I., Henter, Jan Inge, Sönnerborg, Anders, Allander, Tobias, Albert, Jan, Nielsen, Morten, Klingström, Jonas, Gredmark-Russ, Sara, Björkström, Niklas K., Sandberg, Johan K., Price, David A., Ljunggren, Hans Gustaf, Aleman, Soo, and Buggert, Marcus

Abstract

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we 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 broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.

Published
2020

23. Elevated CD21low B Cell Frequency Is a Marker of Poor Immunity to Pfizer-BioNTech BNT162b2 mRNA Vaccine Against SARS-CoV-2 in Patients with Common Variable Immunodeficiency.

Author

Bergman, Peter, Wullimann, David, Gao, Yu, Wahren Borgström, Emilie, Norlin, Anna-Carin, Lind Enoksson, Sara, Aleman, Soo, Ljunggren, Hans-Gustaf, Buggert, Marcus, and Smith, C. I. Edvard

Subjects
*COMMON variable immunodeficiency, *B cells, *COVID-19 vaccines, *HUMORAL immunity, *MESSENGER RNA, *WORD frequency, *PSYCHONEUROIMMUNOLOGY
Abstract

Purpose: Limited data is available on the effect of COVID-19 vaccination in immunocompromised individuals. Here, we provide the results from vaccinating a single-center cohort of patients with common variable immunodeficiency (CVID). Methods: In a prospective, open-label clinical trial, 50 patients with CVID and 90 age-matched healthy controls (HC) were analyzed for SARS-CoV-2 spike antibody (Ab) production after one or two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Additionally, in selected patients, SARS-CoV-2 spike-specific T-cells were assessed. Results: A potent vaccine-induced anti-spike–specific IgG Ab response was observed in all the HC. In contrast, only 68.3% of the CVID patients seroconverted, with median titers of specific Ab being 83-fold lower than in HC. In fact, only 4/46 patients (8.6%) of patients who were seronegative at baseline reached the threshold for an optimal response (250 U/mL). Using the EUROclass definition, patients with either a reduced proportion, but not absolute counts, of switched memory B-cells or having an increased frequency of CD21low B-cells generally generated poor vaccine responses. Overall, CVID-patients had reduced spike-specific IFN-γ positive CD4+ T cell responses 2 weeks after the second dose, compared to HC. The total CD4 and CD4 central memory cell counts correlated with humoral immunity to the vaccine. Conclusions: CVID patients with low frequency of switched memory B-cells or an increased frequency of CD21low B-cells according to the EUROclass definition demonstrated poor responses to Pfizer-BioNTech BNT162b2 mRNA vaccination. Cellular immune responses were significantly affected, affirming that the defect in CVID is not limited to humoral immunity. [ABSTRACT FROM AUTHOR]

Published
2022
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24. Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19

Author

Sekine, Takuya, primary, Perez-Potti, André, additional, Rivera-Ballesteros, Olga, additional, Strålin, Kristoffer, additional, Gorin, Jean-Baptiste, additional, Olsson, Annika, additional, Llewellyn-Lacey, Sian, additional, Kamal, Habiba, additional, Bogdanovic, Gordana, additional, Muschiol, Sandra, additional, Wullimann, David J., additional, Kammann, Tobias, additional, Emgård, Johanna, additional, Parrot, Tiphaine, additional, Folkesson, Elin, additional, Rooyackers, Olav, additional, Eriksson, Lars I., additional, Henter, Jan-Inge, additional, Sönnerborg, Anders, additional, Allander, Tobias, additional, Albert, Jan, additional, Nielsen, Morten, additional, Klingström, Jonas, additional, Gredmark-Russ, Sara, additional, Björkström, Niklas K., additional, Sandberg, Johan K., additional, Price, David A., additional, Ljunggren, Hans-Gustaf, additional, Aleman, Soo, additional, Buggert, Marcus, additional, Akber, Mira, additional, Berglin, Lena, additional, Bergsten, Helena, additional, Brighenti, Susanna, additional, Brownlie, Demi, additional, Butrym, Marta, additional, Chambers, Benedict, additional, Chen, Puran, additional, Jeannin, Martin Cornillet, additional, Grip, Jonathan, additional, Gomez, Angelica Cuapio, additional, Dillner, Lena, additional, Lozano, Isabel Diaz, additional, Dzidic, Majda, additional, Tullberg, Malin Flodström, additional, Färnert, Anna, additional, Glans, Hedvig, additional, Haroun-Izquierdo, Alvaro, additional, Henriksson, Elizabeth, additional, Hertwig, Laura, additional, Kalsum, Sadaf, additional, Kokkinou, Efthymia, additional, Kvedaraite, Egle, additional, Loreti, Marco, additional, Lourda, Magalini, additional, Maleki, Kimia, additional, Malmberg, Karl-Johan, additional, Marquardt, Nicole, additional, Maucourant, Christopher, additional, Michaelsson, Jakob, additional, Mjösberg, Jenny, additional, Moll, Kirsten, additional, Muva, Jagadees, additional, Mårtensson, Johan, additional, Nauclér, Pontus, additional, Norrby-Teglund, Anna, additional, Medina, Laura Palma, additional, Persson, Björn, additional, Radler, Lena, additional, Ringqvist, Emma, additional, Sandberg, John Tyler, additional, Sohlberg, Ebba, additional, Soini, Tea, additional, Svensson, Mattias, additional, Tynell, Janne, additional, Varnaite, Renata, additional, Kries, Andreas Von, additional, and Unge, Christian, additional

Published
2020
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26. Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination: a two-year follow-up of the prospective clinical trial COVAXID.

Author

Chen P, Bergman P, Blennow O, Hansson L, Mielke S, Nowak P, Gao Y, Söderdahl G, Österborg A, Smith CIE, Vesterbacka J, Wullimann D, Cuapio A, Akber M, Bogdanovic G, Muschiol S, Åberg M, Loré K, Chen MS, Ljungman P, Buggert M, Aleman S, and Ljunggren HG

Abstract

Background: Immunocompromised patients with primary and secondary immunodeficiencies have shown impaired responses to SARS-CoV-2 mRNA vaccines, necessitating recommendations for additional booster doses. However, longitudinal data reflecting the real-world impact of such recommendations remains limited., Methods: This study represents a two-year follow-up of the COVAXID clinical trial, where 364 of the original 539 subjects consented to participate. 355 individuals provided blood samples for evaluation of binding antibody (Ab) titers and pseudo-neutralisation capacity against both the ancestral SARS-CoV-2 strain and prevalent Omicron variants. T cell responses were assessed in a subset of these individuals. A multivariate analysis determined the correlation between Ab responses and the number of vaccine doses received, documented infection events, immunoglobulin replacement therapy (IGRT), and specific immunosuppressive drugs. The original COVAXID clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659)., Findings: Several of the patient groups that responded poorly to the initial primary vaccine schedule and early booster doses presented with stronger immunogenicity-related responses including binding Ab titres and pseudo-neutralisation at the 18- and 24-month sampling time point. Responses correlated positively with the number of vaccine doses and infection. The vaccine response was blunted by an immunosuppressive state due to the underlying specific disease and/or to specific immunosuppressive treatment., Interpretation: The study results highlight the importance of continuous SARS-CoV-2 vaccine booster doses in building up and sustaining Ab responses in specific immunocompromised patient populations., Funding: The present studies were supported by the European Research Council, Karolinska Institutet, Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and the Swedish Research Council., Competing Interests: Declaration of interests PB has received honoraria from Takeda and Novartis for educational lectures not directly relevant to this work. SM has received honoraria from Celgene/BMS, Novartis, Gilead/Kite, and DNA Prime for lectures and educational events, and as a member and/or head of data safety monitoring boards from Miltenyi and Immunicum not directly relevant to this work. CIES has received financial support from Moderna for work not directly relevant to this work. KL has received financial support from Moderna for work not directly relevant to this work. PL has received grants from Pfizer, MSD, and personal fees from Takeda, AiCuris, and OctaPharma, not directly relevant to this work. MB has served as a consultant and received honoraria from Oxford Immunotech, Gilead, MSD, BMS, Pfizer, and Mabtech, not relevant to this work. SA has received honoraria for lectures from Gilead with payment to Karolinska University Hospital and Karolinska Institutet, participated in advisory boards/consultation for Gilead and Ribocure with waived compensation not directly related to this work, and reports grants from the Swedish Research Council on COVID-19 vaccination. HGL received honoraria from Sanofi and Vycellix for consultation not relevant to this work, served on the UK-CIC Oversight Committee, led the Karolinska Institutet COVID-19 vaccine group, and is on the scientific advisory group for the International Vaccine Institute. All other authors declare no potential or actual conflict of interest to the work presented in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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27. Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia.

Author

Ingelman-Sundberg HM, Blixt L, Wullimann D, Wu J, Gao Y, Healy K, Muschiol S, Bogdanovic G, Åberg M, Kjellander C, Grifoni A, Sette A, Aleman S, Chen P, Blennow O, Hansson L, Ljunggren HG, Chen MS, Buggert M, and Österborg A

Subjects
Humans, SARS-CoV-2, Adaptive Immunity, Mucous Membrane, Antibodies, Viral, Leukemia, Lymphocytic, Chronic, B-Cell, COVID-19
Published
2024
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28. The Karolinska KI/K COVID-19 Immune Atlas: An open resource for immunological research and educational purposes.

Author

Ljunggren HG, Ask EH, Cornillet M, Strunz B, Chen P, Rao Muvva J, Akber M, Buggert M, Chambers BJ, Cuapio A, Dzidic M, Filipovic I, Flodström-Tullberg M, Garcia M, Gorin JB, Gredmark-Russ S, Hertwig L, Klingström J, Kokkinou E, Kvedaraite E, Lourda M, Mjösberg J, Maucourant C, Norrby-Teglund A, Palma Medina LM, Parrot T, Perez-Potti A, Ponzetta A, Ringqvist E, Rivera-Ballesteros O, Rooyackers O, Sandberg JK, Sandberg JT, Sekine T, Svensson M, Varnaite R, Wullimann D, Eriksson LI, Aleman S, Malmberg KJ, Strålin K, and Björkström NK

Abstract

The Karolinska KI/K COVID-19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS-CoV-2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response towards SARS-CoV-2 infection in humans, as it occurred during the first wave. The Immune Atlas was built as an open resource for broad research and educational purposes. It contains a presentation of the response evoked by different immune and inflammatory cells in defined naïve patient-groups as they presented with moderate and severe COVID-19 disease. The present Resource Article describes how the Karolinska KI/K COVID-19 Immune Atlas allow scientists, students, and other interested parties to freely explore the nature of the immune response towards human SARS-CoV-2 infection in an online setting., (This article is protected by copyright. All rights reserved.)

Published
2022
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