Intranasal BCG cell wall polysaccharide-based subunit vaccine confers protection against Mycobacterium bovis challenge in mice.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), is an important disease affecting livestock and public health. To achieve the goal of ending bTB, more effective vaccines for cattle are urgently needed. Recently, subunit vaccines have attracted widespread attention. An effective bTB subunit vaccine requires the identification of key components in the pathogen that can induce protective immune responses and relies on adjuvants to induce robust immunity against the target pathogen. In this study, we developed subunit vaccines employing BCG cell wall polysaccharides (CW) or Ag85A as antigens, formulated with either chitosan-based nanoparticles (CSNPs) or manganese jelly (MnJ) as adjuvants. The protective efficacy of these vaccines was evaluated following intranasal administration in a mouse model challenged with M. bovis. Our results demonstrated that vaccination with CW-MnJβ elicited a marked IL-17 response. Following M. bovis challenge, the data revealed that CW‑based vaccines (CW‑CSNPs, CW‑MnJα, and CW‑MnJβ) provided significant protection, with CW‑MnJα and CW‑MnJβ showing efficacy comparable to BCG, as evidenced by significant reductions in bacterial burden and obvious alleviation of histopathological damage in the lung and spleen compared to the PBS control. In contrast, Ag85A-based vaccines failed to provide comparable protection, although Ag85A-MnJα and Ag85A-MnJβ stimulated a substantial IgG response. These findings provide evidence that intranasal administration of a subunit vaccine incorporating BCG cell wall polysaccharide as an antigen, adjuvanted with either CSNPs or MnJ, holds substantial promise as an effective bTB vaccine.