Expansion of Proteome-wide Coxiella burnetii Comparative T-cell Epitope Prediction to Include Small Ruminant Hosts

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.