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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1580448
Effective cellular and neutralizing immunity against SARS-CoV-2 after mRNA booster vaccination is associated with pDC and B cell activation
Provisionally accepted
Dorit Fabricius1Carolin Ludwig2
Matthias Proffen2
Janina Hägele2Judith Scholz2Christiane Vieweg2Immanuel Rode3
Simone Hoffmann3
Sixten Körper3
Hubert Schrezenmeier3
Bernd Jahrsdörfer2*- 1Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Ulm, Ulm, Germany
- 2Department of Immune Cell Therapeutics, Institut für Klinische Transfusionsmedizin, Universitätsklinikum Ulm, Ulm, Germany
- 3Institut für Klinische Transfusionsmedizin, Universitätsklinikum Ulm, Ulm, Germany
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Effective SARS-CoV-2 immunity after mRNA booster vaccination hinges on the interplay of cellular and humoral responses. With this study we examined immune mechanisms in individuals receiving a homologous mRNA vaccination regime or heterologous vaccination regimes consisting of combinations of vector and mRNA vaccines. Longitudinal data revealed that mRNA boosters stabilized anti-SARS-CoV-2 IgG titers and neutralization capacities against the wildtype virus and Omicron variants in all cohorts, although the highest efficacy was observed in the homologous cohort. Peripheral B cell frequencies were elevated, and activation markers such as MHC class I/II and CD86 showed significant upregulation post-booster. Plasmacytoid dendritic cells (pDCs), crucial for antigen presentation and release of cytokines with antiviral activity, were also activated and were able to directly enhance antigen-specific T cell activation in functional in-vitro assays. As a result, cellular immunity as reflected by IFN-γ responses in CD4+ and CD8+ T cells, was strongly enhanced in mRNA-based vaccination regimes, thereby contributing to long-term protection. Surprisingly, the number of breakthrough infections was comparable across cohorts, indicating the importance of cellular immunity and pDC activity as compensatory mechanisms for the different humoral response rates in homologous and heterologous vaccination cohorts. By integrating insights from humoral and cellular pathways, this study highlights and confirms the multifaceted nature of vaccine-induced immunity and its particular dependence on B cell, pDC and T cell activation.
Keywords: SARS-CoV-2, COVID-19, mRNA vaccine, Vector vaccine, Comirnaty, Spikevax, Vaxzevria, omicron
Received: 20 Feb 2025; Accepted: 14 Apr 2025.
Copyright: © 2025 Fabricius, Ludwig, Proffen, Hägele, Scholz, Vieweg, Rode, Hoffmann, Körper, Schrezenmeier and Jahrsdörfer. 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: Bernd Jahrsdörfer, Department of Immune Cell Therapeutics, Institut für Klinische Transfusionsmedizin, Universitätsklinikum Ulm, Ulm, Germany
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.