Discovery of CD4+ T cell–recognized B. pertussis antigens that reduce airway colonization
Mohamed M. Shamseldin, Jesse M. Hall, Griffin M. Lawrence, Gabrielle M. Hernandez, Yue Liu, Alexa R. Aubrey, Eva K. Verzani, Rajendar Deora, Amy Lovett-Racke, Jennifer G. Abelin, Purnima Dubey
Mohamed M. Shamseldin, Jesse M. Hall, Griffin M. Lawrence, Gabrielle M. Hernandez, Yue Liu, Alexa R. Aubrey, Eva K. Verzani, Rajendar Deora, Amy Lovett-Racke, Jennifer G. Abelin, Purnima Dubey
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Research Article Immunology Infectious disease

Discovery of CD4+ T cell–recognized B. pertussis antigens that reduce airway colonization

Abstract

Despite widespread vaccination, Bordetella pertussis (Bp) cases are resurging globally. Although CD4+ T cells are known to be essential for sustained protection, the antigens they recognize are not fully characterized, hindering vaccine refinement. Using immunopeptidomics, bioinformatics, and functional T cell assays, we identified high-affinity epitopes from reference and clinical Bp strains presented on MHC-II I-Ab. A subset of these epitopes stimulated systemic and mucosal CD4+ T cells of mice immunized with heat-killed Bp, and peripheral blood T cells from humans vaccinated with the whole-cell pertussis vaccine. Mice immunized with a subunit vaccine comprising two recombinant proteins identified in our screen were subsequently challenged with Bp. Bacterial burden was nearly eliminated from the lower respiratory tract and significantly reduced in the upper respiratory tract. Th1/Th17-polarized CD4+ tissue-resident memory T cells (Trms) were induced in nasal and pulmonary tissues. Depleting memory CD4+ T cells before challenge abolished protection, confirming that antigen-specific CD4+ T cells are critical for clearing Bp from the respiratory tract. Our integrated antigen identification and T cell assay approach revealed previously untested Bp antigens that elicit protective CD4+ T cell–mediated immunity, suggesting that incorporating them into new vaccines may help curb the resurgence of pertussis.

Authors

Mohamed M. Shamseldin, Jesse M. Hall, Griffin M. Lawrence, Gabrielle M. Hernandez, Yue Liu, Alexa R. Aubrey, Eva K. Verzani, Rajendar Deora, Amy Lovett-Racke, Jennifer G. Abelin, Purnima Dubey

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Figure 5

Antigen-specific CD4+ Trms are detected in the lungs and nose of Bp-challenged mice.

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Antigen-specific CD4+ Trms are detected in the lungs and nose of Bp-chal...
(A) Representative gating strategy for antigen-specific tissue-resident memory CD4+ T cells (Trms) in the lungs of Bp-infected mice. NS, nonspecific peptide; peptide 40, representative stimulatory peptide; PMA/I, PMA/ionomycin (positive control). (B–E) Percentages and numbers of CD45–CD4+CD44+CD62L–CD69+ cells producing IFN-γ (B and D) or IL-17 (C and E) in the lungs of Bp536-infected (B and C) and H762-infected (D and E) mice. (F) Representative gating strategy for antigen-specific cytokine-producing Trms in nasal tissue. Cells were stimulated with NS peptide, peptide pool (defined in Figure 3), or PMA/I. (G–J) Percentages and numbers of IFN-γ–producing (G and I) or IL-17–producing (H and J) CD45–CD4+CD44+CD62L–CD69+ cells in the noses of Bp536-infected (G and H) and H762-infected (I and J) mice. Data are mean ± SEM; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared with NS peptide by ANOVA with Dunnett’s post hoc test. Representative of 2 independent experiments.