Disclosure and thanks. Vaccinating Calves: Questions. February 22, Effective Vaccination of Calves

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1 Effective Vaccination of Calves Amelia R. Woolums, DVM MVSc PhD DACVIM DACVM Mississippi State University Starkville, Mississippi, U.S.A. Disclosure and thanks Dr. Woolums and collaborators have received support from: Bayer Animal Health Boehringer Ingelheim Merck Merial Phibro Zoetis Vaccinating Calves: Questions Can immunity of calves be improved by vaccination? Response of calf lymphocytes to mitogenic (nonspecific) stimulation in first week of life How early can you vaccinate calves effectively? What about maternal antibody interference? Data from Kehrli, in Cortese 2009 Calves vaccinated at 8 hours old were protected against Mycobacterium bovis challenge 15 weeks later Buddle et al., 2003 Colostrum deprived calves exposed to coronavirus at 1 day of age were protected against challenge at 3 weeks Heckert et al., 1991 Calves vaccinated with ovalbumin at 2 days of age: antibody at 4 weeks Calves vaccinated with PPD at 2 days of age: skin test positive at 7 weeks Nonnecke et al., 2012 Immune Development, Neonatal Calf Immune response of neonatal calf is functional, but naïve and immature Colostrum is a solution to this problem

2 Before anything else, excellent passive transfer from colostrum is required to establish the basis for strong calf immunity Why We Vaccinate Total Ig IgG IgM Priming vaccine Booster vaccine Vaccines Available For Calves in U.S. Diarrhea E. coli rotavirus coronavirus Salmonella Clostridium Respiratory disease BHV 1 (IBR) BRSV PI3V BVDV Mannheimia haemolytica Pasteurella multocida Histophilus somni Mycoplasma bovis Reproductive disease BHV 1 (IBR) BVDV Leptospira Campylobacter Brucella Miscellaneous Clostridium 7 way (blackleg etc.) rabies Vaccination of calves that have maternal antibody Vaccination of calves with maternal antibody historically considered ineffective Anamnestic (memory) response No response Primary response Time Vaccination without maternal antibody Time Vaccination with maternal antibody

3 In spite of this thinking, research studies indicate calves CAN respond to vaccination even when they have maternal antibody Anamnestic response when maternal antibodies gone Measures of T cell responsiveness in absence of seroconversion Protection against later challenge Vaccination of calves with maternal antibody 2 3 month old beef calves Vaccinated with MLV IBRV + BVDV IBRV SN s 1:19 BVDV SN s 1:35 Control calves not vaccinated Both groups vaccinated again at 6 7 m.o. Menanteau Horta et al, 1985 Calves vaccinated at 2 3 months seroconverted to BVDV IBRV s continued to fall At vaccination at 6 7 months, vaccinated calves seroconverted rapidly to IBRV Significantly higher s than calves not vaccinated at 2 3 months 2-3 months 6-7 months Vaccination of calves with maternal antibody can prime for memory response when maternal antibodies are gone Calf vaccination and antibody responses inactivated vaccines 2 3 month old beef calves IBRV SN s: <1:2 1:128 BVDV 1 SN s: 1:20 1:1920 BVDV 2 SN s: 1:7.5 1:1280 Inactivated IBRV/BVDV/PI3/BRSV Vira Shield 5 ELITE 4 Triangle 4 Control group, no vaccine At 6 7 months of age, calves in Vira Shield group had significantly higher s to IBRV, BVDV 1, and BVDV 2 than control calves Ad i i t ti f i ti t d i d Administration of an inactivated vaccine caused antibodies to stay higher Not all vaccines were equal Boosting may be important Boosted 1 month later Kaeberle et al, 1998

4 Time Vaccination of calves with maternal antibody effect of age Dairy calves vaccinated with M. haemolytica vaccine (Presponse ) 2 and 4 weeks old 6 and 8 weeks old Control group not vaccinated No difference in s at 2 weeks of age Vaccination of calves with maternal antibody can cause antibody s to stay higher Hodgins and Shewen, 1998 At 10 weeks of age, leukotoxin neutralizing s significantly higher in calves vaccinated at 6 and 8 weeks Not significantly higher in calves vaccinated at 2 and 4 weeks Magnitude of and age may impact efficacy of vaccination in young calves with maternal antibody Vaccination of calves with maternal antibody and T cell responses Beef calves vaccinated at 10 days old MLV/inactivated 4 way (CattleMaster 4 ) Control group not vaccinated At 22 days old No difference antibody s Significantly higher lymphocyte responses to IBRV and BRSV in vaccinates Ellis et al, 1996 Vaccination stimulated specific T cells, even though no apparent effect on antibody production Summary Vaccination of calves that have maternal antibody can: Prime for a memory response after maternal antibodies are gone Keep calf serum antibodies higher longer Stimulate T cell responses Not as reliable in calves < 1 month old

5 Vaccination of calves that have maternal antibody: resistance to disease Vaccination and resistance to disease: one example Increased resistance to disease: best measure of value of vaccination Effect has been measured in response to Experimental challenge Naturally occurring disease 4 to 6 week old Holsteins SN s 1:4 1:64 Vaccinated IN once with MLV (hi pass) BRSV Challenged on d. 30 with virulent BRSV Clinical signs evaluated for 7 days BRSV specific IFN g production in several sites evaluated Woolums et al, 2004 Duration of protection following intranasal vaccination may not be long This may be particularly l true for BRSV Disease in calves challenged with BRSV after IN vaccination IFOMA at 3 8 days of age Rectal temperatures measured after BHV-1 challenge Calves vac IN at 3 8 days of age A and B: no maternal antibody to BHV 1 C: maternal antibody to BHV 1 Challenged at 1 month after vac (A) 6 months after vac (B) 3 months after vac (C) Mahan et al., weeks post vac 9 weeks post vac 14 weeks post vac Ellis et al., 2013

6 BHV-1 shedding after BHV-1 challenge Vaccination of Calves: Field Trials Most relevant measure of vaccine efficacy Expensive and logisitically i i ll challenging to conduct Mahan et al., 2016 Field Trial Example #1 27 dairy herds with calf respiratory disease in previous year Evidence of BRSV infection in previous year in 20 9 herds: calves vaccinated with MLV BRSV twice at 4 to 5 week interval 8 herds: calves not vaccinated 10 herds: half calves vaccinated, half not Calves 2 10 months of age at vaccination Vaccinated in August Verhoeff et al., 1984 Calves had low serum s to BRSV at vaccination (78% had no BRSV antibodies) Calves examined by vet weekly from October to January BRSV infection occurred in 6 of 8 nonvaccinated herds 2 of 9 completely vaccinated herds 9 of 10 partly vaccinated herds Signs of respiratory disease seen in 4 of 8 nonvaccinated herds 1 of 9 completely vaccinated herds 1 of 10 partly vaccinated herds Field Trial #1, Key Points MLV BRSV vaccination associated with decreased disease in vaccinated herds INFECTION with BRSV was decreased only when all calves were vaccinated Vaccinating half of calves decreased disease but not infection Calves got 2 doses of vaccine Can t say if 1 dose would have same effect Field Trial Example #2 Weaned beef calves destined for feedlots Single ranch of origin Shipped immediately at weaning OR Kept on farm 45 d., no vac OR Kept on farm 45 d. and MLV viral vac (Titanium 5) and M. haemolytica vac (Presponse) Vac calves boosted 2 weeks later Calves not vac at farm were vac and boosted at feedlot Step et al, 2008

7 Calves kept on ranch 45 days before shipment had significantly lower feedlot respiratory morbidity in first 42 days 6% for weaned 45 d. 10% for weaned 45 d. and vaccinated 35% for shipped immediately No significant difference if calves vaccinated on ranch Health costs (but not total costs) higher for calves shipped immediately No difference for vac vs nonvac groups Field Trial #2, Key Points Vaccination component of a preconditioning program was not related to improved health during receiving period Early weaning before shipment did improve health during receiving period Field Trial, Example #3 468 calves from 3 dairies in Ontario Within each herd, calves randomly assigned to receive IN MLV 3 way vac (Inforce) at 3 6 d of age and again at 6 weeks (n = 215) SC MLV 5 way vac (Bovishield Gold 5) at 6 weeks (n = 211) Control: saline IN both IN and SC at 3 6 d and 6 weeks (n = 42) Treatment groups housed in different areas to prevent transfer of vaccine between groups Calves examined by a veterinarian twice a week for 12 wk Wisconsin respiratory score Thoracic ultrasound Ollivett et al., % of calves had respiratory score 4 at least once Rate of BRD for each group IN vac: 53% SC vac: 59% Control: 33% controls less likely to have BRD than IN or SC (P < 0.05) no difference between vac groups (P > 0.05) 05) 54% of calves had lung consolidation on ultrasound Agreement between clinical signs and US only fair: k = 0.38 Accounting for herd, dystocia, and rib fractures: Odds of consolidation: For SC: 1.6 that of IN (P = 0.03) 0.38 times Control (P = 0.03) For IN 0.23 times Control (P = 0.03) In summary Vaccination had no effect on clinical signs of disease, but decreased risk of lung consolidation IN vac 2x decreased lung consolidation more than SC vac 1x Field Trial #3, Key Points Ultrasound was needed to identify effect of vaccination Also needed to control for farm, dystocia, rib fractures Calves got 2 doses of IN vac vs 1 dose of SC Can t separate effect of vaccination from location Relatively high rate of FPT (TP < 5.2 mg/dl) IN: 48% SC: 31% Control: 21% BUT analysis did not reveal effect of FPT on response to vaccination

8 Case for Discussion 65 head cow calf operation BRD in nursing calves 3 to 4 months old 30% of calves have signs, 2 have died Necropsy of 1 calf: BRSV and Mannheimia Three pregnant heifers purchased from neighbor 2 months ago Case for Discussion Herd evaluation Dam body condition and nutrition acceptable Calving season lasts 5 months Cows not vaccinated or dewormed regularly vaccinated once 2 years ago with killed 5 way Calves not handled until weaning Plan to help limit disease in calves now: Consider treat all calves with long acting antibiotic OR increase surveillance and treat calves with signs of disease Vaccination in face of outbreak? Often done for IBR/PI3 (especially intranasal) May be harmful with BRSV.But often done with apparently no problems Plan to prevent this problem in future: Improve maternal antibody to respiratory viruses in calves Get cows on annual program of 5 way vaccination Try to boost late in pregnancy? Shorten calving season Alternatively, group cows with calves no more than 60 day age range Consider vaccinating calves Plan for vaccinating calves: Time vaccine to occur a month before expected disease onset At 2 months of age in this herd MLV may be best Must be safe for use with pregnant cows If killed, ask rep for data showing efficacy in animals with antibody Consider Mannheimia/Pasteurella vaccine, too TWO doses ideal At 6 weeks and 10 weeks of age (or earlier?) Calf vaccination: take home messages: Young calves can respond to immune stimulation As early as 1 day of life Reliability of response inversely correlated with age Especially in calves with good passive transfer Adult immune responses present by 5 8 months

9 Calf vaccination: take home messages: Passive antibody blocks immune responses sometimes but not always Blocking ggreatest in first month of life Intranasal may be better than injectable in first month Calves 2 3 months old: blocking not much problem Really need more research confirming effect on disease Calf vaccination: take home messages: If vaccinating in first 6 months of life, 2 doses advised 1 2 months between doses Try to time second dose 1 month before expected challenge Calf vaccination: take home messages: BRD vaccines must show efficacy in challenge studies to be licensed But challenge studies are relatively artificial Most available clinical trial evidence supports vaccines for: Mannheimia haemolytica BRSV We need more clinical trials to know how BRD vaccines work in real life