Identification of peptide epitopes in major antigens of Yersinia pestis from infected humans and immunised mice

BACKGROUND: Yersinia pestis (Y. pestis), the bacterial pathogen responsible for plague in humans, remains a public health threat, particularly in light of the recent emergence of antibiotic resistance strains. METHODS: To better understand the immune response against plague and to identify potential targets for immunointervention, we performed an epitope mapping study of the IgG response against a library of peptides representing 18 Y. pestis proteins. The study included sera from 51 individuals who had recovered from plague, 26 uninfected human controls, and 20 sera from mice protected by a live-attenuated vaccine. FINDINGS: Analysis of human sera revealed 32 reactive peptides distributed across eight protein antigens, whereas analysis of mouse sera identified 187 reactive peptides spanning all 18 proteins. Combined analysis of the human and mouse IgG responses to the 32 human-reactive peptides identified 27 B-cell epitopes located within YopD, YopB, LcrV, FyuA, Pla, Ail, Caf1, and PsaA. Of these, one epitope had previously been described as protective and another as immunodominant, whereas the remaining 25 represent immunodominant epitopes identified in this study. INTERPRETATION: Interestingly, IgG antibody responses to selected YopD and YopB peptides were significantly stronger in pneumonic plague than in bubonic plague, suggesting that the distinct clinical manifestations of the disease may be associated with distinct underlying pathophysiological and molecular mechanisms. Our comprehensive mapping of linear IgG epitopes recognised by convalescent human sera, combined with prioritisation based on their predicted neutralising potential, provides a resource for future studies evaluating peptide-based diagnostics, vaccines, and monoclonal antibody therapies against plague. FUNDING: The project was supported by a grant from Agence Nationale de la Recherche (ANR).