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The incidence of whooping cough (pertussis), the respiratory disease caused by Bordetella pertussis (BP) has increased in recent years, and it is suspected that the switch from whole-cell pertussis (wP) to acellular pertussis (aP) vaccines may be a contributing factor to the rise in morbidity. While a growing body of evidence indicates that T cells play a role in the control and prevention of symptomatic disease, nearly all data on human BP-specific T cells is related to the four antigens contained in the aP vaccines, and data detailing T cell responses to additional non-aP antigens, are lacking. Here, we derived a full-genome map of human BP-specific CD4+ T cell responses using a high-throughput ex vivo Activation Induced Marker (AIM) assay, to screen a peptide library spanning over 3000 different BP ORFs. First, our data show that BP specific-CD4+ T cells are associated with a large and previously unrecognized breadth of responses, including hundreds of targets. Notably, fifteen distinct non-aP vaccine antigens were associated with reactivity comparable to that of the aP vaccine antigens. Second, the overall pattern and magnitude of CD4+ T cell reactivity to aP and non-aP vaccine antigens was similar regardless of aP vs wP childhood vaccination history, suggesting that the profile of T cell reactivity in adults is not driven by vaccination, but rather is likely driven by subsequent asymptomatic or sub-clinical infections. Finally, while aP vaccine responses were Th1/Th2 polarized as a function of childhood vaccination, CD4+ T cell responses to non-aP BP antigens vaccine responses were not, suggesting that these antigens could be used to avoid the Th2 bias associated with aP vaccination. Overall, these findings enhance our understanding of human T cell responses against BP and suggest potential targets for designing next-generation pertussis vaccines.

Understanding immune memory to Common Cold Coronaviruses (CCCs) is relevant for assessing its potential impact on the outcomes of SARS-CoV-2 infection, and for the prospects of pan-corona vaccines development. We performed a longitudinal analysis, of pre-pandemic samples collected from 2016-2019. CD4+ T cells and antibody responses specific for CCC and to other respiratory viruses, and chronic or ubiquitous pathogens were assessed. CCC-specific memory CD4+ T cells were detected in most subjects, and their frequencies were comparable to those for other common antigens. Notably, responses to CCC and other antigens such as influenza and Tetanus Toxoid (TT) were sustained over time. CCC-specific CD4+ T cell responses were also associated with low numbers of HLA-DR+CD38+ cells and their magnitude did not correlate with yearly changes in the prevalence of CCC infections. Similarly, spike RBD-specific IgG responses for CCC were stable throughout the sampling period. Finally, high CD4+ T cell reactivity to CCC, but not antibody responses, was associated with high pre-existing SARS-CoV-2 immunity. Overall, these results suggest that the steady and sustained CCC responses observed in the study cohort are likely due to a relatively stable pool of CCC-specific memory CD4+ T cells instead of fast decaying responses and frequent reinfections.