Diversity and T-cell antigenic potentials of Mycoplasma mycoides subsp. mycoides vaccine candidates

Authors: WYNN, EMILY - Orise Fellow; Dassanayake, Rohana; Nielsen, Daniel; Casas, Eduardo; Clawson, Michael

Submitted to: Genome
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2025
Publication Date: 6/3/2025
Citation: Wynn, E.L., Dassanayake, R.P., Nielsen, D.W., Casas, E., Clawson, M.L. 2025. Diversity and T-cell antigenic potentials of Mycoplasma mycoides subsp. mycoides vaccine candidates. Genome. https://doi.org/10.1139/gen-2024-0177.
DOI: https://doi.org/10.1139/gen-2024-0177

Interpretive Summary: Contagious bovine pleuropneumonia (CBPP) is a devastating respiratory disease of cattle that was first described in Europe and subsequently spread to Africa, Asia, Australia, and North America. It currently affects cattle mostly in sub-Saharan African countries where standard control measures are difficult to implement. CBPP is a bacterial disease caused by Mycoplasma mycoides subspecies mycoides (Mmm). There are two vaccines currently in use to control CBPP that both use live, attenuated or weakened strains of Mmm, and are problematic in terms of their efficacies, length of protection, and safety. Consequently, there is need for a new generation of vaccines to use on cattle in sub-Saharan Africa, and to have available for cattle elsewhere in the world in case CBPP were to spread. To that end, genomes of Mmm strains that were isolated from multiple countries and across decades of time were bioinformatically analyzed. Genes that were conserved across the strains were identified, including those that encode outer membrane proteins which can be targeted for vaccine development. Sites within outer membrane proteins with high probabilities of triggering a cellular immune response from cattle were also identified, as they would be particularly beneficial to include in a recombinant Mmm vaccine design. Several proteins had multiple sites, or hot spots, for triggering a desirable immune response that delineate them as potential vaccine candidates. All of the results from this study have been made publicly available for use without restriction in support of the development of new Mmm vaccines.

Technical Abstract: Mycoplasma mycoides subsp mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP), a severe respiratory disease affecting cattle mostly in sub-Saharan African countries. CBPP can cause significant economic losses, and there is a need for efficacious vaccines to help bring the disease under control. To that end, all publicly available non-redundant whole genome sequences of Mmm strains isolated from cattle (n=15) were used to identify a 93% core genome of 806 genes, which included 86 of 208 genes encoding outer membrane and extracellular proteins identified from the literature. Many of them and their encoded protein products were found to be highly conserved at the sequence level, including at the sites of predicted epitope binding with bovine major histocompatibility complex (MHC) Class I and II molecules. Despite the high sequence conservation, multiple proteins had large differences in the numbers of MHC Class I and II epitopes and their predicted binding strengths. These results highlight several promising targets supporting the development of new recombinant protein vaccines for CBPP.