Investigating the overlap between the unexplored T and B cell repertoires in patients having survived a Yersinia pestis infection 3528

Abstract Description Yersinia pestis, the pathogen behind devastating plague epidemics, manifests in bubonic and pneumonic forms. Pneumonic plague has a 60% mortality rate even with prompt treatment, underscoring its potential as a bioweapon. Despite significant research, a safe, effective human vaccine remains elusive. Current vaccine strategies primarily target and investigate F1 and LcrV B cell immunity, protective in mice but inconsistently effective in non-human primates, casting doubt on their human applicability. Cellular immunity against Y. pestis is also critical and may involve antigens distinct from those driving humoral responses, but remains underexplored due to methodological challenges. This study evaluated T-cell responses in plague survivors by stimulating T cells with Y. pestis lysate and examining antigenic overlap with humoral responses. We used 292 linear peptides, representing 0.01% of the Y. pestis proteome, known for eliciting strong humoral responses. Results showed a significantly higher Yersinia-specific T-cell response in survivors (Mann-Whitney, p = 0.0465); exposed individuals were 27.8% more responsive to plague lysate than controls. Importantly, only part of this response was linked to tested tested humoral peptides (p = 0.0027), F1 (p < 0.0001), or LcrV (p = 0.0017). These findings underscore the crucial importance of our ongoing study to sequence activated T-cell variable regions following stimulation and characterize the naturally acquired T-cell repertoire. Funding Sources Institut Pasteur of Madagascar Internal funding Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)