Navigating immune evasion: The quest for an effective Mycoplasma bovis vaccine.

Mycoplasma bovis (M. bovis) is a globally significant pathogen, causing substantial economic losses to the cattle industry through pneumonia, mastitis, and arthritis. Despite persistent efforts, the development of a consistently effective vaccine remains elusive. This review synthesizes progress across inactivated, attenuated live, and subunit vaccine platforms, highlighting that even promising candidates yield only partial and inconsistent protection. We argue that these shortcomings arise from two principal, intertwined obstacles: the absence of a standardized framework for assessing vaccine efficacy, encompassing unified challenge models, validated immune correlates, and well-defined endpoints, and the pathogen's remarkable ability to subvert diverse host immune defense mechanisms. Consequently, achieving robust protection necessitates a paradigm shift. A deeper mechanistic understanding of host-pathogen interactions, coupled with the strategic application of reverse vaccinology and precise gene-editing technologies, will be essential to design next-generation vaccines that can finally overcome M. bovis immune evasion.