Proteome-wide analysis of Coxiella burnetii for conserved T-cell epitopes with presentation across multiple host species

Authors: Piel, Lindsay; Durfee, Codie; White, Stephen

Submitted to: BMC Bioinformatics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2021
Publication Date: 6/2/2021
Citation: Piel, L.M.W., Durfee, C.J., White, S.N. 2021. Proteome-wide analysis of Coxiella burnetii for conserved T-cell epitopes with presentation across multiple host species. BMC Bioinformatics. 22. Article 296. https://doi.org/10.1186/s12859-021-04181-w.
DOI: https://doi.org/10.1186/s12859-021-04181-w

Interpretive Summary: Coxiella burnetii is a bacterial agent that causes disease in both ruminant livestock (cows, goats, and sheep) and people. At present, there is not an available vaccine within the United States to help to prevent the economic loss that ensues when ruminant species are infected, nor is there a licensed vaccine for human use. Economic loss is characterized by late-term abortions, inflammation within the udder affecting milk production, and decreased weight of animals that are born alive. In order to promote vaccine generation, this article uses bioinformatic techniques, or trained computer programs, to help determine what proteins made by the bacteria will engage the immune system of the host. This is the first attempt at identifying Coxiella burnetii proteins that interact with a ruminant immune system, leveraging recent "training" of computational resources to handle cattle. Furthermore, this research marks the initial attempt to characterize every protein produced by the bacterium, instead of previous research which has focused on a specific subset of proteins. Within this work there were 55 novel proteins suggested to interface well with the immune systems of cattle, human, and mouse. Future work with these proteins will determine if they are able to incite the appropriate immune response and afford protection of not only our agricultrual animals, but possibly humans as well.

Technical Abstract: Background: Coxiella burnetii is the Gram-negative bacterium responsible for Q fever in humans and coxiellosis in domesticated agricultural animals. Previous vaccination efforts with whole cell inactivated bacteria or surface isolated proteins confer protection but can produce a reactogenic immune responses. Thereby a protective vaccine that does not cause aberrant immune reactions is required. The critical role of T-cell immunity in control of C. burnetii has been made clear, since either CD8+ or CD4+ T cells can empower clearance. The purpose of this study was to identify C. burnetii proteins bearing epitopes that interact with major histocompatibility complexes (MHC) from multiple host species (human, mouse, and cattle). Results: Of the annotated 1,815 proteins from the Nine Mile phase I RSA 493 assembly, 402 proteins were removed from analysis due to a lack of inter-isolate conservation. An additional 391 proteins were eliminated from assessment to avoid potential autoimmune responses due to the presence of host homology. We analyzed the remaining 1,022 proteins for their ability to produce peptides that bind MHCI or MHCII. MHCI and MHCII predicted epitopes were filtered and compared between species yielding 777 MHCI epitopes and 453 MHCII epitopes. These epitopes were further examined for presentation by both MHCI and MHCII, and for proteins that contained multiple epitopes. There were 31 epitopes that overlapped positionally between MHCI and MHCII across host species. Of these, there were 9 epitopes represented within proteins containing >=5 total epitopes, where another 24 proteins were found to incorporate a similar number of total epitopes. In all, 55 proteins were found to contain high scoring T-cell epitopes. Besides the well-studied protein Com1, all the identified proteins were novel when compared to previously studied vaccine candidates.