What happens in the lymph node after mRNA vaccination? In eBioMedicine, the Infection and Immunity group at IRB, led by Prof. Santiago F. González, identifies plasmacytoid dendritic cells as contributors both to the humoral and cell mediated (CD8⁺ T-cell) responses induced by the Pfizer-BioNTech BNT162b2 vaccine.
The Pfizer-BioNTech coronavirus vaccine (BNT162b2) was among the first nanoparticle-based vaccines approved by the World Health Organisation (WHO) and demonstrated 95% efficacy against SARS-CoV-2 infection. Despite its success, the precise immune mechanism behind its effectiveness remains poorly understood. This study investigated, using a preclinical mouse study, the early immune responses occurring in the draining lymph node (dLN) following vaccination.
The study reveals that the coronavirus vaccine was rapidly transported to the dLN, where it was predominantly captured by leukocytes that subsequently expressed the SARS-CoV-2 spike protein. Among these cells, plasmacytoid dendritic cells (pDCs) emerged as regulators involved in both inflammatory and humoral immune responses. Single-cell transcriptomic profiling revealed active interactions between pDCs and CD8+ T cells. Functional in vivo studies further demonstrated that pDCs promoted CD8+ T-cell activation and expansion, indicating an involvement in shaping adaptive immunity following vaccination.
These findings identify pDCs as antigen-presenting cells involved in coordinating the immune response to BNT162b2. By regulating both innate and adaptive immune pathways and facilitating CD8+ T-cell activation, pDCs appear to play a functional role in the efficacy of this mRNA vaccine. This study provides additional insights into the immunological processes underlying the mechanism of action of mRNA vaccines and may inform the future design and optimization of mRNA-based therapies.
Link to the scientific article:
Role of plasmacytoid dendritic cells in humoural and CD8(+) T-cell memory responses following BNT16…
Pizzichetti, C. Latino, I. Virgilio, T. Capucetti, A. Chahine, K. Cascione, L. Moro, S. G. Bilato, G. Brugger, M. Kozarac, N. Pulfer, A. Renner, L. Thakur, R. S. Benarafa, C. Legler, D. F. Gonzalez, S. F.
in EBioMedicine (2026) Vol.131 pp106432
