1. HIGH IMMUNE RESPONSE TECHNOLOGY
GENETIC REGULATION OF THE BOVINE IMMUNE SYSTEM
PRACTICAL APPLICATION OF THE
HIGH IMMUNE RESPONSE TECHNOLOGY
IN DAIRY HEALTH MANAGEMENT
Professor Bonnie A. Mallard
University of Guelph

2. Current Challenges for Dairy Health
Mastitis costs the dairy producer between $110 to $320 per case and 1 out of every 5 dairy quarters in Canada is infected with mastitis- causing pathogens
Canadian Bovine Mastitis Network, University of Montreal, Quebec, Canada
Emerging and re-emerging diseases, many of which are zoonotic;
Tomley and Shirley Phil. Trans. R. Soc. B. 364:2637
There are increasing restrictions on antibiotic use in livestock
Berge et al., J.Dairy Sci. 92:4707
Several dairy support industry companies offer diagnostic, treatment or prevention solutions for specific diseases
However, there are No solutions available on the market for evaluating & predicting broad-based disease resistance

3. Genetic Selection for Better Health
Genetic selection by immune response is desirable and sustainable for reducing infectious disease
Kelm et al Vet. Clin. North Am. Food Anim. Prac. 17:477
Stear et. al., Res. Vet. Sci. 71:1
Genetic selection to improve immune response provides health and productivity advantages
Wilkie and Mallard Vet. Immunol. Immunopath. 72:231
Mallard th Proc. Am. Assoc. Bovine Practitioners. Sept 20-21, Vancouver British Columbia, 40:1-7.
Reviews by Kelm et al and Stear et al. And Wilkie et al. Demonstrate that it is possible to improve immune response and disease resistance through genetic selection using EBV.
Selection in this vain have been successful in mice, guinea pigs, pigs, and the same is also true for cattle. First, variation in immune response must be identified

4. The High Immune Response (HIR) concept was first developed in pigs
Mallard, B.A., B.N. Wilkie, B.W. Kennedy and M. Quinton
Use of estimated breeding values in a selection index to breed Yorkshire pigs for high and low immune and innate resistance factors.
Anim. Biotech. 1992, 3:

5. GUIDING PRINCIPLE
Optimal Disease Resistance Should be a Function of Optimal Innate and Acquired Defence Mechanisms
Phenotype

6. What is HIR for Dairy Cattle?
The High Immune Response (HIR) is:
Simple immune response test
Done once in an animal’s lifetime
Helps producers identify their healthiest animals
HIR cows are at much less risk for disease
Is a useful management tool to improve health
Is heritable - useful for breeding h2=
Novel alternative to use with traditional methods of infection control

7. THE HIR TEST PROTOCOL
DAY 14
- CMIR - Initiate skin thickness
test and take background
skin-fold measurements
- AMIR - Collect blood for ELISA
DAY 15
- Final skin-fold measurements
hours
DAY 0
- Collect blood for ELISA
- Immunize with type 1 & 2 antigens in neck or rump
The HIR test is a 15 day test that requires 3 farm visits:

8. Ranking Animals using Estimated Breeding Values
Measure the IR phenotype
Phenotype = Genotype + Environment
Calculate a breeding value to rank animals
EBV = Phenotype – Environment
Integrating these quantitative genetic
methods is a useful way to rank
animals to enhance the immune system
and improve disease resistance

9. TWO IMMUNE TESTS ARE PERFORMED TO REPRESENT BROAD-BASED RESISTANCE
CELL-MEDIATED IMMUNE RESPONSE
(CMIR)
ANTIBODY MEDIATED IMMUNE RESPONSE
(AMIR)
Photos and figures courtesy of Dr. B. Mallard 9

10. Immune Response Can Be Used to Rank Cattle
− High
− Avg
− Low
− Mean
Sera AMIR Response to OVA
Optical Density Value (OD)
During my master`s work we investigated variation in Antibody response during the peripartum period from wk -8 to wk +6, and developed an index to categorize response and evaluate disease.
Group 1 = high
Group 2= average
Group 3 = low
Week relative to calving
Wagter and Mallard et al J. Dairy Sci. 83:488

11. Breeding Values for IR in Canadian Herds
Combined EBVs for AMIR and CMIR of Holstein Cows in 58 Canadian Bovine Mastitis Research Network Cohort Herds
Day 14 – Primary Response
Day 21 – Secondary Response 85 90 95
100
105
110
115
Low
Average
High
Time of immune response sampling
Thompson-Crispi et al 2011 Technical Report to the Genetic Evaluation Board, Canadian Dairy Network

12. Disease by Combined AMIR/CMIR Rank
HIR Benefit #1 – Lower Disease Occurrence
Disease by Combined AMIR/CMIR Rank
Odds Ratios for High vs Average Cows:
2x less mastitis
4x less metritis
1.4x less ketosis
1.3x less retained placenta
This graph represents the combined disease infections and metabolic comibine health data from my study and Jason`s.
What this represents is that Cattle that are HIR have 2x less disease occurrence than LIR
Disease data from: Wagter et al JDS 83:488 and De Lapaz, J MSc Thesis, University of Florida.
Thompson-Crispi, K. et al., Technical Report to the Genetic Evaluation Board, Canadian Dairy Network

13. HIR Benefit #2 – Better Response to Commercial Vaccines
LsMEANS OF SERUM ANTIBODY TO J5 E. coli VACCINE
Ref – Wagter & Mallard et al 2000 JDS 83:488

14. HIR Benefit #3 – Greater Amount of Antibody in Colostrum
HIGH RANK FOR SERUM ANTIBODY ALSO MEANS THE HIGHEST RANK FOR WHEY ANTIBODY
Ref – Wagter & Mallard et al 2000 JDS 83:488

15. HIR Benefit #4 – Cost Benefit for HIR Cattle
There is a 3-FOLD benefit in terms of reduced disease/treatment costs relative to the predicted cost of test in the first year
Reduced disease costs were calculated based on a comparison of risk for disease between HIR and AVG cows
Costs calculated using the Odd Ratios and current available economic cost estimates
Increase to a 12-FOLD return on investment by the fourth year

16. Bringing HIR to the Marketplace
Quantitative Market Assessment
1000 dairy producers were sent a letter to participate
N=128 producers participated in survey
116 on line (Survey Monkey) and 12 by mail
Producers were asked about their operation, management priorities and attitudes towards health and interest in HIR
Survey and analysis completed by Agri-Studies, an agricultural marketing firm in Guelph, Ontario

17. Determining Disease Prone Animals

18. Dealing with Disease Prone Animals

19. Producers were Read an HIR Concept Statement
“Researchers have developed a new testing process for dairy cows that allows you to determine which cows in your herd have a greater ability to resist a variety of common diseases like mastitis, ketosis, milk fever and Johne’s disease...
And then asked some further questions

20. Producers Identify Benefits of HIR

21. Producer Interest in HIR

22. Potential Uses of HIR

23. Sire Can Also Be HIR Tested
No adverse reactions and no cross-reactivity were found
before and after HIR testing protocol

24. Summary Producers are Interested in HIR as a management tool
Cattle (cows, calves and sires) may be ranked by immune response based on animal variation (EBV)
Antibody response in sera is highly correlated in whey
HIR testing in sires demonstrates variability in immune response, with no adverse effects or cross-reactivity
Beta-testing and evaluation of knowledge transfer of HIR will help to improve interest and the adoption of HIR by the dairy industry

25. Acknowledgements Collaborator Bruce Wilkie Filippo Miglior Ken Leslie
Jack Dekkers
Students and PDFs
Lauri Wagter-Lesperance
Kathleen Thompson-Crispi
Armando Hernandez
Doug Hodgins
Brad Hine
Maria Nino-Soto
Industry Collaborators
CDN
CanWestDHI
Gencor
Semex Alliance
Agri-Studies
Technical Support
Shannon Cartwright
Laura Cain
Sophia Lim
Funding Support NSERC
OMAFRA
DairyGen
Business Development Office, U of G

26.
Questions?