Whooping cough disease induces durable protection from asymptomatic re-infection 2310171

Abstract Introduction Bordetella pertussis (BP) is the causative agent of whooping cough (WC), also known as pertussis, a highly contagious respiratory disease. Although BP vaccination remains the most effective preventive measure, the shift from whole-cell pertussis (wP) vaccine to acellular pertussis (aP) vaccines has been associated with the resurgence of pertussis cases in many countries. While differences in immune responses between wP and aP vaccines have been well documented, limited information exists regarding BP-specific memory T cell responses, particularly against the broad range of BP antigens not included in aP vaccine formulations. Methods This study investigates BP-specific responses in donors vaccinated with aP or wP in childhood, as well as donors clinically diagnosed with whooping cough. To identify BP-specific CD4 T cells we stimulated PBMCs with two pools of peptides: one pool encompassing peptides from aP vaccine antigens (including FHA, PRN, PT, and FIM2/3), and a second pool containing peptides from non-aP vaccine antigens. Results Our findings reveal differential BP antigen reactivity based on vaccination and infection history, with notably high reactivity to non-aP vaccine antigens in the aP-vaccinated cohort, suggesting prevalent subclinical colonization. Unexpectedly, adults examined years after recovery from clinical disease showed lower T cell responses. In contrast, robust BP-specific IgG responses were observed in acute and convalescent pediatric donors, suggesting that individuals who experienced symptomatic disease can develop a strong humoral immunity and remain protected from reinfections. Single-cell RNA and T cell receptor sequencing analyses are currently being performed to further elucidate qualitative differences in immune responses to vaccination versus infection. Conclusion This study emphasizes the importance of understanding immune responses to both subclinical and clinical BP infection for identifying specific immune profiles that correlate with protection. Funding Source This project has been funded in part with Federal funds from the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (Grants No. U19 AI142742) Topic Categories Vaccines and Immunotherapy (VAC)