Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of...
Transcript of Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of...
![Page 1: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/1.jpg)
Fasciola hepatica Vaccine
Update
Grace Mulcahy UCD School of Veterinary Medicine
![Page 2: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/2.jpg)
![Page 3: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/3.jpg)
Why Vaccines?
• Cattle and sheep of all ages
• Clinical and sub-clinical effects
• Immune compromise
• The drugs don’t work (sometimes)
![Page 4: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/4.jpg)
Leg Brick vs Lego City
Virus vs. Helminth Parasite
![Page 5: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/5.jpg)
Immunoregulation by Fluke
• Mice
• Cattle, Sheep Salmonella? Clostridial Diseases?
![Page 6: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/6.jpg)
Fh Mb
![Page 7: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/7.jpg)
The Challenge of Vaccination
Outcome
Protective responses
Immune distortion
![Page 8: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/8.jpg)
What Does a Fluke Vaccine Need to Do?
• Protect against natural
challenge
• Prevent/reduce loss of
productivity
• Block transmission
• Reduce need for drug
treatment
• Prevent immunoregulation
![Page 9: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/9.jpg)
Candidate /Experimental Vaccine
Antigens – Recombinant
• Cathepsin L1 (Cathepsin L3)
• Cathepsin B
• Peroxiredoxin
• Leucine amino-peptidase
• Fatty-acid binding protein
• Glutothione-S-transferase
![Page 10: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/10.jpg)
Leucine Amino-peptidase
• High levels of
protection in sheep
• IgG1 and IgG2
• Relatively short-lived
antibody responses
Maggioli et al., Vaccine 29: 8057-9063 2011
![Page 11: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/11.jpg)
Recombinant Mutant CL1
gastrodermal epithelial cells
Pro-CL1
rmFhCL1
Properties of FhCL1
– Acquire nutrients by breaking down proteins to peptides
– Degrades interstitial matrix proteins
– Involved in immuno evasion mechanism
– Suppress Th1 response
FhCL1
Peter R. Collins et al. 2004
![Page 12: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/12.jpg)
FhCL1 in Previous Experiments
Trial Research Species Antigen Reduction
fluke burden (%)
Dalton et al. 1996 Cattle FhCL1, FhCL2 FhCL1+FHb FhCL2+FHb
53.7
72.4
Mulcahy et al. 1998 Cattle FhCL2+FHb 72
Piacenza et al. 1999 Sheep FhCL1, FhCL2 FhCL1+FhCL2
33 60
Van Milligan et al. 2000 Rats FhCL3 intra-peritoneally 92,6
Kofta et al. 2000 Rats cDNA encoding Fh.Cysteine
protease 74
Wedrychowicz et al. 2003 Calves Lambs
cDNA intranasally 54.2 56.5
Golden et al. 2010 Cattle rmFhCL1 48.2
![Page 13: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/13.jpg)
Small Scale Vaccine Field Trial – rFhCL1
V1- 6 weeks
Confirm absence of fluke infection
0 V1
+3 weeks V2
+6 weeks Onto fluke pasture together
+20 weeks Slaughter & count flukes in livers
![Page 14: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/14.jpg)
Protection in low-challenge field
trial 15
5.384.85
0
2
4
6
8
10
12
14
16
Control Adj A Adj B
Flukes
Golden et al. 2010).
![Page 15: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/15.jpg)
Assays for Protective Antibodies - Avidity
Control V1 V2
Golden et al., 2010 Vaccine 28: 5551-5557
[KSCN] needed to reduce antigen-
antibody binding by 50%
Chaotropic Assay
![Page 16: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/16.jpg)
![Page 17: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/17.jpg)
Macrophage Activation
![Page 18: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/18.jpg)
Paravac
University College Dublin – Ireland
![Page 19: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/19.jpg)
Large Scale Clinical Trial in Cattle
> 200 animals Different age-groups
Vaccinated
Matched Controls
Followed for 2 years And/or slaughtered as per commercial
requirements
![Page 20: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/20.jpg)
Experimental Plan
• Animals from three
Irish farms where
liver fluke is known
to be present (all
belong to Teagasc
Institute)
![Page 21: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/21.jpg)
Johnstown Castle– Quantitative ELISA
Titration of IgG1 and IgG2 Responsesfg
![Page 22: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/22.jpg)
Cumulative Faecal Eggs
Vaccinates Controls
No. of Pos Samples
Cumulative Egg Counts 99 187
32 42
![Page 23: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/23.jpg)
Faecal Eggs – Frequency Distribution
0
10
20
30
40
50
60
70
0 1-4 5-9 10-14 15-19 20-24 25-29
Vax
Control
![Page 24: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/24.jpg)
Vaccines are a Realistic Goal
• Liver Fluke Systems Biology
• Liver Fluke Genetics
• Interactions of Drug treatment and vaccination
• Interactions of immunoregulation and vaccination
A Vaccine is more than an antigen or even an antigen cocktail
![Page 25: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/25.jpg)
![Page 26: Fasciola hepatica Vaccine Update...Fasciola hepatica Vaccine Update Grace Mulcahy UCD School of Veterinary Medicine Why Vaccines? •Cattle and sheep of all ages •Clinical and sub-clinical](https://reader030.fdocuments.net/reader030/viewer/2022040614/5f09ffa17e708231d42984fb/html5/thumbnails/26.jpg)
Thanks to…..
Olwen Golden Elaine McCarthy Olwen Golden Mary Sekiya Laura Garza-Cuartero Jack O’Sullivan Andres Campo Andreas Chryssafidis