Total respiratory tract immunization induces optimal systemic and regional antigen-specific immune responses 2244163
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Abstract Introduction Respiratory infections represent a major global health challenge. Different intranasal vaccine strategies can target specific areas of the respiratory tract, which may influence local and systemic immune responses. Methods Here, we combined peptide-major histocompatibility complex class I and II (pMHCI and pMHCII) tetramers with flow cytometry and single cell RNA sequencing (scRNAseq) to comprehensively study spike-specific CD8+ and CD4+ T cells following immunization with SARS-CoV2 spike protein. Following intramuscular (IM) priming with spike protein and poly:IC, we compared different boosting strategies - upper respiratory tract (URT), total respiratory tract (TRT), and IM. Results At 4 weeks post-boost, the number of spike-specific CD4+ and CD8+ T cells was higher in the lungs of mice receiving TRT boosting compared to URT or IM boosting. We also observed higher frequencies and numbers of CD4+ and CD8+ resident memory T cells (TRM) in the lungs of TRT versus URT or IM groups. In the nasal mucosa (NM), both TRT and URT boosting resulted in higher frequencies of spike-specific CD4+ and CD8+ TRM cells than IM. Notably, TRT was the only boost strategy that induced serum and lung spike-specific IgA. However, despite generating fewer spike-specific T cells and antibodies than TRT, URT boosting still protected mice against viral challenge. Moreover, both spike-specific CD4+ and CD8+ T cells obtained from the NM expressed higher levels of IFN-g, and spike-specific CD8+ T cells in the NM produced higher levels of granzyme B compared to those cells recovered from lung and spleen. Finally, scRNAseq analysis with barcoded tetramers revealed that epitope specificity influenced CD4+ T cell differentiation resulting in epitope-specific T helper cell bias. Conclusion In sum, TRT boosting enhanced lung immunity and epitope-driven CD4+ T cell phenotypes offer a promising approach to guide optimized vaccine design. Funding Source NIH P01 AI165072 AND AMERICAN LUNG ASSOCIATION CA-1252074 Topic Categories Mucosal and Regional Immunology (MUC)
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Total respiratory tract immunization induces optimal systemic and regional antigen-specific immune responses 2244163
- Date Crossref
- 28/07/2026
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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Harvard University, Massachusetts General Hospital et Broad Institute, avec 6 autres affiliations.
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