Bovine Respiratory Mycoplasmas and the Commensal-Pathogen Continuum: A Systematic Review of Vaccines and Diagnostic Approaches

Mycoplasmas colonise bovine respiratory mucosal surfaces as commensal organisms, yet certain species may contribute to bovine respiratory disease complex (BRDC) when host and environmental conditions favour pathogenic expression. Clinical outcome is context-dependent, with species ranging from assumed true commensals (M. arginini, M. bovirhinis) to pathobionts (M. bovis) and less frequently reported species (M. alkalescens, M. canadense) and an opportunist (M. dispar). The absence of a synthesis applying a commensal-pathogen continuum framework to bovine respiratory mycoplasmas while jointly evaluating carriage, vaccine performance, and diagnostic interpretability represents a key gap. The objective of this paper is to evaluate available evidence on vaccination, diagnostics, and control of bovine respiratory mycoplasmas within a commensal-pathogen continuum framework. The preparation of this paper followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 and synthesis without meta-analysis (SWiM) guidelines. PubMed, Scopus, and Web of Science were searched through 12 December 2025. Of 6119 records identified, 212 studies met predefined Population, Intervention, Comparator, Outcome, Study design (PICOS) criteria and were classified into four domains: carriage and prevalence (n = 73), diagnostic performance (n = 71), pathogenesis and immune evasion (n = 53), and vaccine efficacy (n = 15). Risk of bias was assessed using domain-appropriate tools. Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. M. bovis dominated the literature (199/212; 93.9%), reflecting concentrated research investment, with M. dispar (22; 10.4%), M. bovirhinis (19; 9.0%), M. arginini (4; 1.9%), M. canadense (1; 0.5%), and M. alkalescens (1; 0.5%) also well documented. M. bovirhinis and M. arginini were consistently recovered from clinically healthy cattle, supporting their classification as true commensals. M. bovis exhibited pathobiont behaviour. Nasopharyngeal carriage was reported in 18-58% of healthy cattle and progressed to clinical disease (estimated 15-40%) in a context-dependent manner. Whole-cell bacterins demonstrated inconsistent efficacy, whereas virulence-factor vaccines showed more consistently positive outcomes. Future vaccines targeting conserved virulence-associated antigens and designed to elicit mucosal immunity may provide higher levels and more consistent protection than conventional whole-cell bacterin formulations. The majority of diagnostic studies detected mycoplasma presence without distinguishing colonisation from causation. Bovine respiratory mycoplasma species occupy distinct positions on the commensal-pathogen continuum, with direct implications for vaccine design, diagnostic interpretation, and disease control. Integrated control combining syndrome-aligned diagnostics and targeted vaccination was the approach most consistently supported by the available evidence.