Expansion of proteome-wide Coxiella burnetii comparative T-cell epitope prediction to include small ruminant hosts

Authors: Grossman, Paige; Schneider, David; KIRKPATRICK, ROBERT - Washington State University; WHITE, STEPHEN - Former ARS Employee; Piel, Lindsay

Submitted to: Cellular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2023
Publication Date: 12/22/2023
Citation: Grossman, P.C., Schneider, D.A., Kirkpatrick, R., White, S.N., Piel, L.M. 2023. Expansion of proteome-wide Coxiella burnetii comparative T-cell epitope prediction to include small ruminant hosts. Cellular Immunology. 5(5):143-161. https://doi.org/10.33696/immunology.5.180.
DOI: https://doi.org/10.33696/immunology.5.180

Interpretive Summary: Coxiella burnetii is the causative agent of Q fever, a human disease that can be acquired from livestock and for which no vaccine is approved for use in the United States. In this study, bioinformatic analysis was used to predict which proteins of C. burnetii are likely to interact with two elements of the adaptive immune system--that part of the immune system responsive to vaccination--of cattle, sheep, and goats. Each protein was divided into short peptide segments, and the strength of predicted interactions was categorized as strong, weak, or non-binding. Two-hundred-six and seven-hundred-sixty-six peptides were predicted to interact with one of these immune system elements across all three species. Fifty-one peptides were predicted to interact with both elements across all three species. These results provide a rational prioritization of peptides to develop a safe and perhaps broadly effective C. burnetii peptide-based vaccine.

Technical Abstract: Background Coxiella burnetii is the causative agent of Q fever, a human disease that can be acquired from livestock. Diseases caused by this organism have caused great losses in livestock and human health. No vaccine is approved for use in the United States, and formalin-inactivated whole-cell vaccines pose a significant manufacturing risk for biocontainment. A subunit vaccine using recombinant peptides from C. burnetii would be safer and less resource-intensive to produce. This study used reverse vaccinology to expand our prediction sets of T-cell epitopes for the major histocompatibility complex (MHC) Class I and II alleles of cattle, sheep, and goats. Thereafter, the present results were compared with those from our previous prediction sets for mice and humans. Results Small ruminant breed representation for the United States was ensured by querying whole genome sequences on the National Center for Biotechnology Information database. Consequently, twenty-two sheep MHC Class I, seventeen goat MHC Class I, and one goat MHC Class II alleles were added to the analyses, resulting in a total of fifty-six sheep MHC Class I, eighteen goat MHC Class II, and twenty-seven goat MHC Class II alleles. Predicted interactions of C. burnetii proteome-derived peptides with each MHC allele were categorized as strong, weak, or non-binding based on bioinformatic scores. Interspecies comparisons resulted in 256 peptides of interest for MHC Class II presentation and 766 peptides of interest for MHC Class I presentation. Of these, 51 peptides were predicted to bind with both classes of MHC alleles, of which 33 were newly identified. Conclusion The high scoring T-cell epitope predictions identified in this study provide grounds for prioritizing subunit candidates to further develop a safe and perhaps broadly effective C. burnetii vaccine.