A recombinant BCG vaccine induces specific immunity against respiratory syncytial virus and <i>Mycobacterium bovis</i> in calves in a field study

Respiratory infections in calves are a serious problem, particularly as maternal antibodies wane and calves become susceptible to respiratory pathogens, such as bovine respiratory syncytial virus (bRSV) and <i>Mycobacterium bovis</i> (<i>M. bovis</i>), which are two important pathogens affecting animal production. Although there are currently vaccines available against bRSV, their protection is limited. Regarding <i>M. bovis</i>, no vaccines are presently commercially available. However, BCG is being tested experimentally as a vaccine against this microbe. Here, we evaluated the safety and immunogenicity of the rBCG-N-hRSV vaccine against bRSV and <i>M. bovis</i> in 120 <i>Polled Hereford</i> calves in a field study. Each group, consisting of 30 calves, received either rBCG-N-hRSV, a commercial vaccine against bRSV, WT-BCG against <i>M. bovis</i>, or placebo. Calves, aged 14-21 days- received a first dose (day 0), followed by a booster 14 days later. Safety was evaluated by monitoring local and systemic adverse effects and potential transmissibility of the vaccine. Altogether, immune responses against both pathogens were characterized at 0, 14, 28, and 180 days after the first vaccination. The results indicate that rBCG-N-hRSV is safe and elicits a significant increase in antigen-specific IgG2 and IgA antibodies, accompanied by proliferation of CD8⁺ and γδ TCR⁺ T cells, resulting in an antigen-specific activation profile and memory CD4⁺ T cells that remained elevated up to 180 days post-vaccination. These findings suggest that rBCG-N-hRSV elicits a specific immune response against bRSV and <i>M. bovis</i> under field conditions.