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: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 11/25/2024
Publication Date: 1/2/2025
Citation: Wynn, E., Dassanayake, R., Nielsen, D., Casas, E., Clawson, M. 2025. Diversity and T-cell antigenic potentials of Mycoplasma mycoides subsp. mycoides vaccine candidates [abstract]. Research Workers in Animal Diseases Conference Proceedings. p. 105. Available: https://crwad.org

Interpretive Summary:

Technical Abstract: Objective: Mycoplasma mycoides subsp mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP). CBPP is a severe respiratory disease of cattle in sub-Saharan African countries where it causes significant economic losses and there is a need for efficacious vaccines to help bring it under control. To that end, we used publicly available sequences of Mmm strains isolated from cattle to identify the core genome of Mmm, compare the sequence diversity of proteins known or predicted to be outer membrane or extracellular, and to predict epitope binding sites for bovine major histocompatibility complex (MHC) proteins. Methods: All publicly available, non-redundant genomes of Mmm in GenBank were downloaded for this study (n = 15). The genomes represent strains isolated from Europe, Africa, Asia, and Australia within the 20th or 21st centuries that all likely emerged from a European ancestor within the last 300 years. They were annotated with DFAST, and core and pan genome analyses were performed using the bioinformatic software package EDGAR. Two hundred and eight known or predicted outer membrane or extracellular proteins of Mmm were identified from the literature and their sequences were compared at the community level. Regional epitope binding efficiencies of these proteins to bovine MHC Class I and II were predicted with NetMHCpan and NetMHCIIpan. Results: The 15 Mmm genomes have a 94% core genome of 793 genes. Eighty-six of the 208 genes encoding outer membrane and extracellular proteins identified from the literature are present in the core genome. A majority of those genes and their encoded proteins products are highly conserved at the sequence level, including at the sites of predicted epitope binding with bovine MHC Class I and II. Despite the high sequence conservation, multiple proteins have large differences in the numbers of MHC Class I and II epitopes and their predicted binding strengths. Conclusions: This study underscores the importance of core genome analyses when characterizing targets for vaccine studies. The high conservation of protein sequences across the 15 Mmm genomes and their predicted epitope sequences provide opportunities for the development of new diagnostic and preventive mitigation measures, including new vaccines. Additionally, the genes of several vaccine protein candidates identified in previous studies were not part of the core genome and may not provide efficient protection across diverse Mmm populations. However, despite the geographical diversity of the strains represented in this study, their genomes are unlikely to represent the complete diversity of extant Mmm in Africa. Consequently, sequencing more contemporary strains could better direct future vaccine work.