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Impact of BVDV vaccination programs USAHA Subcommittee on BVDV Kansas City Paul H. Walz Department of Pathobiology

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Page 1: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Impact of BVDV vaccination programs

USAHA Subcommittee on BVDVKansas City

Paul H. WalzDepartment of Pathobiology

Page 2: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Genus Pestivirus - 2008– BVDV 1 (11 subgenotypes; BVDV 1a; BVDV 1b)– BVDV 2 (2 subgenotypes; BVDV 2a)– Hog cholera virus (classical swine fever virus)– Border disease virus (BDV-1; BDV-2; BDV-3)– Giraffe 1, Pronghorn, Reindeer-1 (BDV-2), Ho_Bi

Genus Pestivirus - 2018– Pestivirus A: BVDV 1 (21 subgenotypes)– Pestivirus B: BVDV 2 (4 subgenotypes)– Pestivirus C: CSFV– Pestivirus D: BDV– Pestivirus E: Pronghorn antelope pestivirus– Pestivirus F: Bungowannah virus– Pestivirus G: Giraffe pestivirus– Pestivirus H: Hobi-like pestivirus– Pestivirus I: Aydin-like pestivirus– Pestivirus J: rat pestivirus– Pestivirus K: atypical porcine pestivirus

Page 3: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Efficacy of viral reproductive vaccinesBVD virus

Page 4: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

BVDV Vaccination: Fetal Infection

MLV

KV

0.15

MLV and KV

Page 5: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)
Page 6: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Vaccination provides the best protection when the best products are administered at the best times

Grooms DS, Givens MD, Sanderson MW, et al., Bovine Practitioner 43(2):106-116;2009

Page 7: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

=Bull breeding=Estrus synchronization

Wean 75 heifer calves 

(5 to 7 m of age)

Day 0

BVDV PI exposure (Days 715 to 731)

TAI(Day 214)

Vaccination: Group A received MLV. Group B received CV.Group C received saline. 

183 366 738

IV inoculation with BoHV‐1

830 978

Pregnancy status assessed on Days 731, 746, 774, 802, 830 and

subsequently every two weeks (Days 746 to 978) until all cows

aborted or calved.

TAI(Day 620)

Last calf due to be born following 

dual virus exposure

Calving

491 554

Pregnancy Check(Day 345)

Abortion/calving

Vaccination: Groups A and B received MLV. Group C received saline. 

//

Vaccination: Group A received MLV. Group B received CV.Group C received saline. 

Pregnancy Check(Day 711)

Figure 1. Design of research to assess efficacy of revaccination with multivalent modified-live viral (MLV) or combination viral (CV; temperature-sensitive MLV BoHV-1 and killed BVDV ). The study was initiated with 30 heifers in Treatment Group A, 30 heifers in Treatment Group B, and 15 heifers in Treatment Group C. m = months; TAI = timed artificial insemination; BVDV = bovine viral diarrhea virus; PI = persistently infected; IV = intravenous; BoHV-1 = bovine herpesvirus-1.

Funded by Zoetis

Page 8: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Antibody Titers to Bovine Viral Diarrhea Virus 2 (Strain 125c)

Page 9: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Immunity acquired by booster vaccination with KV viral vaccine following priming vaccination with MLV viral

vaccine prior to breeding is transferred to the nursing calf

Page 10: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Antibody Titers to Bovine Herpesvirus-1 (Colorado Strain)

Page 11: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Detection of BVDV and BoHV-1 in Fetuses and Calvesa = abortion after BVD exposure but before inoculation with BoHV-1A = abortion after BVDV exposure and inoculation with BoHV-1C = live calfRed =BVDVBlue = BoHV-1Black = both viruses

**Significant difference detected among treatment groups for samples cumulatively.

Page 12: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Vaccines for bovine reproductive pathogens must provide fetal and abortive protection against Bovine viral diarrhea virus (BVDV).

Safety concerns associated with MLV vaccines have led some producers to utilize only KV vaccines in prebreeding and annual revaccination herd health programs.

Thus, a comparative assessment of the fetal and abortive protective efficacy resulting from pre-breeding vaccination of cows with different KV vaccines is needed.

Funding provided by Zoetis Animal Health

Page 13: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

0 21

Vaccinate: Group A: CattleMaster® Gold FP®5; Spirovac®L5Group B: ViraShield® 6 + L5 HBGroup C: Triangle™ 10 HBGroup D: Control (saline)

42 101

Bull breeding

129

Preg √

133 161 325 384

Assess pregnancy status every three weeks (days 161-384) until all cows aborted or calved

BVDV PI Exposure (28 days)

135 198

Bull breeding

418 481231 259

92 pregnant cows

28 cows

Assess pregnancy status every three weeks (days 251-487) until all cows aborted or calved

Calving

Calving

9 PIs (3 each of 1a, 1b, 2a)

3 PIs (single 1a, 1b, 2a)

122 beef heifers and

cows

18 pregnant cowsPreg √

220

Page 14: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

PI AnimalBVDV 

genotypeserum nasal swab serum nasal swab

11 1b 6.25 x 104 6.25 x 104 2.0 x 104 6.25 x 104

12 2 3.51 x 105 2.0 x 105 2.0 x 104 6.25 x 104

18 2 3.51 x 103 2.0 x 105

28 2 4.86 x 103 3.51 x 105

32 1a 6.25 x 103 3.51 x 104 3.51 x 103 3.51 x 104

34 1a 6.25 x 103 2.0 x 104 3.51 x 103 6.25 x 104

285 1b 6.25 x 104 3.51 x 104 6.25 x 103 6.25 x 103

407 1a 3.51 x 103 2.0 x 104 3.51 x 102 3.51 x 104

819 1b 2.0 x 103 6.25 x 104 2.0 x 103 2.0 x 104

3/16* 2 6.25 x 104 3.51 x 105 6.25 x 103 6.25 x 104

Day 133, 4/26/16 Day 161, 5/24/16

* 02May2016

died: 23May2016died: 28Apr2016

PI AnimalBVDV 

genotypeserum nasal swab serum nasal swab

12 2 6.25 x 103 6.25 x 104 2.0 x 104 6.25 x 104

32 1a 3.51 x 104 3.51 x 104 3.51 x 103 3.51 x 104

285 1b 3.51 x 105 2.0 x 105 6.25 x 104 6.25 x 103

Day 231, 8/2/16 Day 259, 8/30/16

Page 15: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

100%

CONTROL (SALINE)

≤ 48 ─ 32≥ 64

Proportion of study cows (n=110) with antibody titers directed against BVDV 2 (125c) at the onset of challenge

3%

45%52%

CATTLEMASTER® GOLD FP®5; SPIROVAC®L5

94%

6%

VIRASHIELD® 6 + L5 HB

51%39%

10%

TRIANGLE™ 10 HB

Page 16: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Proportion of cows with at least one positive result for BVDV on WBC passage between day 6-10 of exposure

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

CattleMaster® GoldFP®5; Spirovac®L5

ViraShield® 6 + L5 HB Triangle™ 10 HB Control (saline)

Page 17: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

CattleMaster® GoldFP®5; Spirovac®L5

ViraShield® 6 + L5 HB Triangle™ 10 HB Control (saline)

Persistently Infected (PI) No evidence of BVDV transplacental infection

Infection Results – Fetuses and Calves (n=104)

43% 93% 60% 100%

Page 18: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

CattleMaster® GoldFP®5; Spirovac®L5

ViraShield® 6 + L5 HB Triangle™ 10 HB Control (saline)

Persistently Infected (PI) No evidence of BVDV transplacental infection

Infection Results – Live-born Calves (n=92)

35% 92% 57% 100%

Page 19: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Total Number of BVDV genotypes by Group

13 PIs from 31 pregnancies

27 PIs from 32 pregnancies

18 PIs from 31 pregnancies

15 PIs from 16 pregnancies

3

2

02468

10121416182022

CattleMaster® GoldFP®5; Spirovac®L5

ViraShield® 6 + L5HB

Triangle™ 10 HB Control (saline)

1a 1b 2a

Page 20: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

BVDV1a-NADL

BVDV1a-Singer

BVDV1c-Bega

BVDV1c-Trangie

AuPI407

AuPI34

AuPI32

AuPI11

BVDV1b-NY-1

BVDV1b-TGAN

AuPI819

AuPI285

BVDV2b-VS-63

BVDV2b-VS123.4

AuPI12

AuPI3 16

BVDV2a-890

BVDV2a-1373

AuPI28

AuPI18

0.0000.0500.1000.150

Number of Progeny Pis (n=73)

11

76

810

7

258

BVDV 1b(24)

BVDV 2a(40)

BVDV 1a (9)

Page 21: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Calving

BVDV PI Exposure (28 days)

=Group D

=Group C=Group A

=Group B

164 182 185 195 197 204 257 266 269 290 295 307

Sequence of Abortion – All cows (110 pregnancies – 18 abortions)Note: Number below arrow indicates study day

Calving

BVDV PI Exposure (28 days)

=Group D

=Group C

175 182 185 195 197 204 257 266 269 290 295 307

Page 22: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Current Situation:• Large commercial dairy farms experiencing BVDV

• Utilizing 4 doses of MLV prior to first breeding

• Two doses as calves (35 and 80 days of age)

• 150 days of age• 30 days prior to breeding

• Multiple PI calves in 1st calf heifers • Approaching 2% prevalence 

• BVDV 1b subgenotype

Page 23: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Table 1. Current BVDV vaccines. (MLV = modified-live viral; KV = killed viral; cp = cytopathic)

Vaccine  Manufacturer  Formulation  BVDV 1a strain  BVDV 2 strain 

Express 5  Boehringer Ingelheim Vetmedica, Inc. (BIVI)  MLV  Singer (cp)  296 (cp) 

Pyramid 5  BIVI  MLV  Singer(cp)  5912 (cp) 

Boviehield Gold 5  Zoetis  MLV  NADL (cp)  53637 (cp) 

Titanium 5  Elanco  MLV  C24V (cp)  296 (cp) 

Vista 5 SQ  Merck  MLV  Singer (cp)  125A (cp) 

MaterGuard 5  Elanco  KV  C24V (cp)  125c (cp) 

Triangle 5  BIVI  KV  Singer (cp)  5912 (cp) 

CattleMaster Gold FP  Zoetis  KV  5960 (cp)  53637 (cp) 

ViraShield 6  Elanco  KV  K22 (cp)GL760 (ncp)  TN131 (ncp) 

 

Page 24: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

GENOTYPE Tajima & Dubovi:

Bulk milk samples from 16 herds & 37 infected 

cattle

40%

49%

11%

Fulton: 1,263 PI cattle entering a feedlot (4‐years)

9.7%

12%

78.3%

Page 25: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)
Page 26: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Vaccination

Immunization

Prevention of Infection

Is the increasing frequency of BVDV 1b identification the result of failure to

vaccinate, failure to immunize, or failure to prevent fetal infection?

Page 27: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Control of Bovine Viral Diarrhea Virus in Ruminants

ACVIM-LA Consensus Statement2018 Update

Page 28: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

BVDV infections in Ruminants – 2018 ACVIM LA Consensus Statement

Consensus Statement 2018 Panel

• Paul Walz, Auburn University• Manuel Chamorro, Kansas State University• Shollie Falkenberg, USDA NADC• Thomas Passler, Auburn University• Frank van der Meer, University of Calgary• Amelia Woolums, Mississippi State University

Page 29: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Consensus Statement Purpose

“Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with

guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of a Consensus Statement is evidence-based medicine, but if such evidence is

conflicting or lacking, the panel provides interpretive recommendations based on their collective expertise.

BVDV infections in Ruminants – 2018 ACVIM LA Consensus Statement

Page 30: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

BVDV infections in Ruminants – 2018 ACVIM LA Consensus Statement

Critical areas for discussion - 2008• Genotypic, biotypic, and antigenic variation• Pathogenesis• Infection in heterologous species – reservoirs

and interspecific transmission• Effective BVDV control

– Diagnosis– Vaccination– Biosecurity

• Eradication

Page 31: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

BVDV infections in Ruminants – 2018 ACVIM LA Consensus Statement

Evaluation of science on controlling BVDV – 2018What are major points?

• Genotype and antigenic variation– Diversity of strain types– Vaccination-escape viruses

• Pathogenesis – foundation of immunosuppression• Effective BVDV control

– Diagnosis– Vaccination

• Safety and efficacy• Inclusion of BVDV 1b in current vaccines

– Biosecurity• Eradication – is it possible in North America

Page 32: Impact of BVDV vaccination programs - USAHA...=Bull breeding =Estrus synchronization Wean 75 heifer calves (5 to 7 m of age) Day 0 BVDV PI exposure (Days 715 to 731) TAI (Day 214)

Questions?

[email protected]