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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1447555
This article is part of the Research Topic SARS-CoV-2 Vaccines Beyond the Pandemic Era View all 4 articles

mRNA-1273 vaccination induces polyfunctional memory CD4 and CD8 T cell responses in patients with solid cancers undergoing immunotherapy or/and chemotherapy

Provisionally accepted
Anastasia Gangaev Anastasia Gangaev 1Yannick van Sleen Yannick van Sleen 2Nicole Brandhorst Nicole Brandhorst 3Kelly Hoefakker Kelly Hoefakker 3Bimal Prajapati Bimal Prajapati 4Amrita Singh Amrita Singh 4Annemarie Boerma Annemarie Boerma 4Marieke van der Heiden Marieke van der Heiden 4Sjoukje F. Oosting Sjoukje F. Oosting 5Astrid A. van der Veldt Astrid A. van der Veldt 6T Jeroen N. Hiltermann T Jeroen N. Hiltermann 7Corine H. GeurtsvanKessel Corine H. GeurtsvanKessel 8Anne- Marie C. Dingemans Anne- Marie C. Dingemans 9Egbert F. Smit Egbert F. Smit 10Elisabeth G. de Vries Elisabeth G. de Vries 11John B. Haanen John B. Haanen 3Pia Kvistborg Pia Kvistborg 3Debbie van Baarle Debbie van Baarle 4*
  • 1 Division of Molecular Oncology and Immunolog, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands
  • 2 Division of Molecular Oncology and Immunolog, University Medical Center Groningen, Groningen, Netherlands, Netherlands
  • 3 Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands
  • 4 Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, Groningen, Netherlands, Netherlands
  • 5 Department of Medical Oncology, University Medical Center Groningen, Groningen, Netherlands, Netherlands
  • 6 Department of Medical Oncology and Radiology & Nuclear Medicine, Cancer Institute, Erasmus Medical Center, Rotterdam, South Holland, Netherlands
  • 7 University Medical Center Groningen, Groningen, Netherlands, Netherlands
  • 8 Department of Viroscience, Cancer Institute, Erasmus Medical Center, Rotterdam, South Holland, Netherlands
  • 9 Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, Netherlands
  • 10 Department of Thoracic Oncology, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands
  • 11 Department of Medical Oncology, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands

The final, formatted version of the article will be published soon.

    Research has confirmed safety and comparable seroconversion rates after SARS-CoV-2 vaccination in patients with solid cancers. However, the impact of cancer treatment on vaccineinduced T cell responses remains poorly understood. In this study, we expand on previous findings within the VOICE trial, and evaluate the functional and phenotypic composition of mRNA-1273-induced T cell responses in patients with solid tumors undergoing immunotherapy, or/and chemotherapy, and individuals without cancer. ELISpot analysis of 386 participants showed a robust induction of spike-specific T cell responses 28 days after full vaccination irrespective of treatment with similar response rates ranging from 75% to 80%.Further in-depth characterization of identified spike-specific T cell responses using flow cytometry in a subset of 63 participants revealed a distinctive cytokine production pattern across all cohorts, with CD4 T cells producing IFNγ, TNF, and IL-2, while CD8 T cells produced IFNγ, TNF, and CCL4. Spike-specific CD4 T cells displayed cohort-specific variations characterized by a higher proportion of monofunctional cells producing TNF in individuals without cancer and patients treated with chemotherapy alone, whereas patients treated with immunotherapy alone or chemoimmunotherapy predominantly produced IFNγ.Nevertheless, polyfunctional spike-specific memory CD4 and CD8 T cell responses were comparable across cohorts. Interestingly, immunotherapy-treated patients exhibited expansion of spike-specific CD4 T cells with a terminally differentiated effector memory phenotype.Overall, these findings highlight that systemic treatment in patients with solid tumors does not compromise the quality of polyfunctional mRNA-1273-induced T cell responses, underscoring the importance of COVID-19 vaccination in patients with solid cancers undergoing systemic treatment.

    Keywords: SARS-CoV-2-specific T cells, COVID-19, Cancer, Immunotherapy, chemotherapy

    Received: 11 Jun 2024; Accepted: 08 Aug 2024.

    Copyright: © 2024 Gangaev, van Sleen, Brandhorst, Hoefakker, Prajapati, Singh, Boerma, van der Heiden, Oosting, van der Veldt, Hiltermann, GeurtsvanKessel, Dingemans, Smit, de Vries, Haanen, Kvistborg and van Baarle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Debbie van Baarle, Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, Groningen, 9713, Netherlands, Netherlands

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.