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Disease Protection and Immunogenicity of Two Commercial Intranasal Vaccines Evaluated with a BHV-1 Challenge of Weaned Beef Calves
Bolton, M.; Griebel, P.; Hill, K...
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Objective: This study compared both immunogenicity and disease protection between 2 commercial intranasal vaccines (Nasalgen IP® and Inforce 3®), when used in beef calves and challenged with BHV-1.
Materials and Methods: One hundred, 4 to 10 week-old calves at processing were randomly assigned to five intranasal treatment groups (n = 20/group): Group A - vaccine diluent at processing and weaning, Group B – NasIP (Nasalgen IP® ) at processing and booster at weaning; Group C – vaccine diluent at processing and primary NasIP at weaning; Group D- Inf3 (Inforce 3®), at processing and booster at weaning; and Group E –vaccine diluent at processing and primary Inf3 at weaning. The analysis of BHV-1 serum neutralizing anti- body titres confirmed IN vaccination was performed with maternal antibodies present. All calves were removed from dams at 5- 6 months of age and 14 healthy, BVDV negative calves from each group were shipped the same day from the ranch to the research station. The day after arrival, calves received the designated weaning vaccination. Three days later all calves were aerosol challenged with BHV-1 and monitored daily for clinical respiratory signs, body weight, and rectal temperature. Nasal secretions and serum samples were collected to quan- tify innate and acquired immune responses.
Results: Analyses of clinical responses following BHV-1 challenge revealed mean rectal temperatures among all vaccinated animals were significantly (p≤0.0001) lower than animals receiving diluent. Weight loss following BHV-1 infection was reduced compared to controls in all vaccination groups (p<0.0001). Differences in temperature and weight were significant among vaccination groups but were numerically small.
Over the duration of the study all vaccinate groups shed less virus than the diluent control calves. Inf3 booster vaccination significantly (p=0.0008) reduced virus shedding when comparing to primary Inf3 vaccination. NasIP booster group shed significantly (p<0.0007) less virus beginning on day 4 post-infection. However, a significant reduction in virus shedding was not observed until day 5 post-infection with both Inf3 booster vaccination (p=0.0001) and NasIP primary vaccination (p=0.03). The primary Inf3 vaccination significantly reduced virus shedding only on day 6 (p=0.04) and day 9 (p=0.001) post-infection and this group did not significantly (p=0.197) reduce the number of days virus was shed compared to the control group. In contrast, NasIP primary (p=0.017), NasIP boost (p=0.0007), and Inf3 boost (p<0.0001) significantly reduced the number of days on which individual animals shed virus.
IFN alpha and gamma secretion was significantly (p<0.0001) lower in all vaccinate groups compared to the control group. Both booster groups had significantly lower IFN alpha and IFN gamma secretion (p<0.0001) compared to primary vaccination groups.
The NasIP booster group was the only group displaying a significant increase in BHV-1 serum IgG antibody titres three days after booster vaccination compared to controls (p<0.0001) and all other vaccine groups (p<0.0003). There were no significant differences in BHV-1-specific IgA antibody responses among treatment groups during the post challenge period (p=0.60).
Conclusions: Differences in primary and boostered groups demonstrated that NasIP and Inf3 intranasal vaccination of young calves, when neutralizing maternal antibody was present in blood, induced BHV-1 specific immune memory that persisted for at least 4 months in the upper respiratory tract, evident primarily as significantly greater reductions in body temperature and IFN secretion post challenge. Primary vaccination with NasIP resulted in a more rapid onset of reduction in virus shedding compared to primary vaccination with Inf3 and primary NasIP vaccination resulted in a significant reduction in the number of days virus was shed but primary Inf3 vaccination did not. When comparing booster vaccination with NasIP and Inf3 there were small but significant differences in clinical disease but not virus shedding. The NasIP booster group was the only group to show a significant (p=0.0003) increase in specific serum IgG three days after booster vaccination.
Keywords: Intranasal vaccines, BHV-1, protection, immunogenicity.
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Affiliation of the authors at the time of publication
Veterinary Consultant, Michigan, MI, United States;
Intervac University of Saskatchewan, Saskatchewan, Canada;
Merck Animal Health, Madison, NJ, United States;
MSD Animal Health, Boxmeer, Netherlands.
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