Ruminants & Swine JAVMA | MAY 15, 2021 | VOL 258 | NO. 10 1119 B ovine respiratory disease continues to impair animal welfare and cause substantial economic losses owing to morbidity, reduced performance, and death of cattle in both the beef and dairy indus- tries. 1 Total prevention of BRD remains an elusive goal. Vaccination is an important adjunct to improve- ments in management, nutrition, and biosecurity. For some animals, such as young calves with circulating maternal antibodies, vaccine administration by the IN route may result in a superior immune response than vaccine administration by other routes. Indeed, Innate and acquired immune responses of colostrum-fed neonatal Holstein calves following intranasal vaccination with two commercially available modified-live virus vaccines Lowell T. Midla VMD Kevin L. Hill DVM Nicholas K. Van Engen DVM, PhD Matthew Edmonds DVM, PhD David G. Renter DVM, PhD Marshall N. Streeter PhD John P. Hutcheson PhD Philip J. Griebel DVM, PhD From Merck Animal Health, Madison, NJ 07940 (Midla, Hill, Streeter, Hutcheson); Johnson Research LLC, Parma, ID 83660 (Van Engen, Edmonds); Department of Diag- nostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 (Renter); and Vaccine and Infectious Disease Organization (VIDO)–Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada (Griebel). Address correspondence to Dr. Midla (Lowell.Midla@ Merck.com). OBJECTIVE To compare immune responses induced by 2 commercially available vac- cines with a bovine herpesvirus type 1 (BHV1) component following intra- nasal (IN) administration to colostrum-fed calves. ANIMALS 90 male Holstein calves (ages, 5 to 14 days). PROCEDURES In a randomized complete block design, each calf received 2 mL (1 mL/ nostril) of vaccine A (n = 30), vaccine B (30), or saline (0.9% NaCl) solution (30) on day 0. Blood samples were collected for determination of serum anti-BHV1 IgG titer, and nasal fluid (NF) samples were collected for deter- mination of interferon (IFN)- α and IFN-γ concentrations and for secretory IgA titers against BHV1, Mannheimia haemolytica, and Pasteurella multocida at predetermined times for 42 days after vaccination. RESULTS All calves were seropositive for anti-BHV1 IgG, and the mean anti-BHV1 IgG titer did not differ significantly among the 3 groups at any time. Both vaccines induced significant transient increases in NF IFN- α and IFN-γ con- centrations. On day 5, mean IFN- α concentration and the proportion of calves with detectable IFN- α concentrations for the vaccine A group were significantly greater than those for the vaccine B and control groups. On day 42, the mean NF anti– P multocida IgA titers for both vaccine groups were significantly greater than that of the control group. CONCLUSIONS AND CLINICAL RELEVANCE Both vaccines induced innate and acquired immune responses in calves with colostral antibodies. The magnitude of the IFN- α response and proportion of calves with detectable IFN- α differed between the 2 vaccine groups. Both vaccines appeared to enhance the IgA response against P multocida. ( J Am Vet Med Assoc 2021;258:1119–1129) IN administration of MLV vaccines is used in many cattle production systems, and several commercial vaccines have been licensed for IN administration to cattle. 2 Administration of MLV vaccines by the IN route induces acquired immune responses includ- ing antibody and cell-mediated immunity to specific pathogens, 3–9 and some MLV vaccines labeled for IN administration also invoke innate immune responses characterized by the production of IFNs. 3,4 In bovids, there are 3 distinct subtypes of IFNs (type I [9 α and 3 β genes], type II [1 γ gene], and type III [1 λ gene]), which have the capacity to inhibit the replication of many viruses. 4,10,11 In some situations, it may be beneficial to stimulate the innate immune system (manifested in part by the production of IFNs) of animals to increase their resistance to viral infec- tions. 12 In a study 11 in which BHV1-naïve calves were experimentally infected with BHV1, concentrations of IFN- α, IFN- β, and IFN- γ in nasal secretions became increased from baseline concentrations within 2 to 3 days after infection, peaked at approximately 5 days after infection, and returned to baseline concentra- ABBREVIATIONS BHV1 Bovine herpesvirus type 1 BRD Bovine respiratory disease BRSV Bovine respiratory syncytial virus IFN Interferon IN Intranasal MLV Modified-live virus NF Nasal fluid TBS Tris-buffered saline tgD Truncated form of recombinant BHV1 glycoprotein D TP Total protein Unauthenticated | Downloaded 03/01/23 08:06 AM UTC