Bovine respiratory disease (BRD) is a multifactorial and polymicrobial disease impacting the cattle industry, often affecting young calves. Additionally, calves undergoing pneumonia are constantly treated with antibiotics, raising concerns for future antimicrobial resistance. Bovine viral diarrhea virus 2 (BVDV2) and Bovine herpesvirus 1 (BHV1), play significant role in BRD pathogenesis. Prevention strategies include Modified-live virus (MLV) vaccines. These MLV have demonstrated to prevent from clinical disease. Intranasal vaccination is considered a promising tool for priming young calves. Additionally, trace minerals are important components of antioxidant enzymes and vital microelements for growth, health, immunity, and reproduction. Trace minerals have been reported to improve humoral and cell-mediated immune responses. The main objectives of this dissertation were to evaluate the effects of supplementation with trace minerals, compare the available routes for MLV vaccination, and examine the role of the humoral and cell-mediated immunity induced in protection against BRD pathogens. Moreover, we investigated the effect of trace mineral supplementation along with MLV vaccination on the induction of immunity and its correlation to the level of protection against challenge with BVDV2 and BHV1. The first study, calves treated with ITM had significantly higher BRSV-SNA titers on day 14 (p = 0.045), and day 28 (p = 0.028) than control calves. In the second study,unvaccinated calves developed significant leukopenia than vaccinated calves. Moreover, calves treated with ITM and IN booster had a higher number of circulating CD8+ T cells. In contrast, calves receiving SC booster vaccination had a higher number of circulating CD4+ T cells. In the third study, calves in the unvaccinated group presented higher lesion scores by endoscopic examination, five days after BHV1 challenge than for calves receiving ITM plus vaccination (either SC or IN route; p < 0.01). The findings from this dissertation provided new insights about booster vaccination route in dairy calves. Further, the results indicated that ITM enhanced the immune response when delivered at priming and booster vaccination. Finally, this dissertation generated multiple new questions that need to be addressed in future research projects to define the role of vaccine immunity and improve viability of cattle rearing and management.