Bovine respiratory disease (BRD) ranks among the most prevalent and economically burdensome diseases affecting the global dairy cattle industry, primarily resulting from co-infection with multiple pathogens, including Mycoplasma bovis (M. bovis) and bovine alphaherpesvirus type 1 (BoAHV-1). Despite the availability of vaccines, promoting their immunogenicity to deliver rapid, effective protection remains a critical challenge. The non-pathogenic probiotic Escherichia coli Nissle 1917 (EcN) has exhibited immunomodulatory properties related to digestive health; however, its potential as an adjuvant in bovine respiratory applications remains unexplored. In this study, we investigated the role of EcN as an immune enhancer in dairy calves for the first time, emphasizing its effects on both innate and adaptive immune responses when administered alongside an M. bovis-BoAHV-1 vaccine. Our findings revealed that all calves maintained normal clinical signs following EcN administration. Compared to the blank control, EcN treatment significantly upregulated natural immune markers. Furthermore, the combination of EcN with the M. bovis-BoAHV-1 vaccine elicited superior adaptive responses, evident in the boosted intensity and duration of both cellular and humoral immunity. Under experimental challenge conditions, the EcN-treated vaccinated group showed a more robust specific immune response, along with lower pathogen shedding titers and shorter duration compared to calves receiving the combined vaccine alone. In conclusion, EcN can safely and effectively activate the innate immune response of dairy calves, improving the adaptive immune response induced by a combined vaccine. Our findings represent the first confirmation of EcN's applicability in BRD and offer a novel strategy for enhancing vaccine protective efficacy.IMPORTANCEBovine respiratory disease is a major cause of economic losses in the global cattle industry, partly because of the delayed efficacy of current vaccines. This study investigated the intranasal administration of the probiotic Escherichia coli Nissle 1917 to enhance bovine immunity. The results illustrated that this probiotic safely activated the innate immune system, bridging the gap in protection between vaccination and the development of specific immune responses. When paired with a combined vaccine targeting Mycoplasma bovis and bovine alphaherpesvirus type 1, the probiotic significantly elevated protective antibody levels and reduced pathogen shedding and duration. These findings introduce an innovative non-antibiotic strategy for enhancing respiratory health in the cattle industry, providing a valuable tool to improve disease resistance and potentially reduce reliance on antimicrobial drugs.
Zhang et al. (2026) studied this question.