Bovine respiratory disease (BRD) causes significant economic losses in dairy calves. Induction of an early immune response via parenteral vaccination is complicated by the interference of colostral immunity. In this study, we investigated early immunization against selected conserved bacterial antigens. Calves were vaccinated twice intranasally and then subcutaneously with Histophilus somni recombinant proteins (rOMP40 or rHsp60) mixed with one of two adjuvants: CpG ODN2007 or MPLA. The control group (Con) was treated with PBS. The first immunization was done between 24 and 48 h of life and then twice in two weeks intervals. Blood, nasal, and saliva secretion samples were collected directly before vaccination (S1-S3) and then on 42-44 (S4) and 59-61 (S5) day of life. Antibodies (IgG/IgG/IgM/IgA in serum; IgG/IgA in secretions) against both vaccine antigens were quantified in all samples. Intranasal and subcutaneous vaccinations using the described formulas did not increase antibody reactivity against the tested proteins. The reactivity of serum IgG, IgM, and IgA anti-rOMP40 antibodies was significantly higher in S1 in all groups than that in the other samplings (p˂0.01). Significant differences in the reactivity of serum anti-rOMP40 antibodies between groups were identified in S1 (IgA reactivity was higher in the CpG vs. MPLA group; p < 0.05), S4 (IgM reactivity was higher in Con vs. CpG group; p < 0.05), and S5 (IgG1 reactivity was higher in MPLA vs. Con group; p < 0.05). The lack of consistent changes in antibodies after immunization (S4 and S5) hinders the drawing of conclusions regarding the effect of immunization on antibody reactivity. In the future, establishing a proper immunization window and adjuvants for nasal vaccines against bacterial pathogens causing BRD in calves remains to be determined.