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1. Vaccination of cattle with Escherichia coli O157:H7-derived proteins results in humoral and cellular immune responses but does not confer protection against subsequent challenge. Katie Boland DVM, PhD June 15, 2013. 2. E. Coli O157:H7. Causes disease in humans Diarrhea (MMRW, 1985)

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katie boland dvm phd june 15 2013

1

Vaccination of cattle with Escherichia coli O157:H7-derived proteins results in humoral and cellular immune responses but does not confer protection against subsequent challenge

Katie Boland DVM, PhD

June 15, 2013

e coli o157 h7

2

E. Coli O157:H7
  • Causes disease in humans
    • Diarrhea (MMRW, 1985)
    • Hemolytic-uremic syndrome (HUS) (Riley LW, Remis RS, Helgerson SD, et al, 1983)
      • Renal failure, hemolytic anemia and thrombocytopenia
  • Pathogenesis
    • Attaching and effacing (A/E) lesions
      • Pedestal formation
      • Dissolution of brush border
    • Shiga toxins
  • Prevention is key
reservoir

3

Reservoir
  • Cattle are major source of contamination (Armstrong et al., 1996)
    • Transient colonization
    • Variable shedding
      • Meat
      • Produce
      • Water
  • Recto-anal junction
    • Lymphoid rich tissue
pre processing control

4

Pre-processing control
  • Decontamination
  • Probiotics
  • Diet
  • Antimicrobials

Vaccination

http://www.chadcompany.com/MVC-006F.JPG

a e lesions

5

A/E lesions

(Gauthier, Finlay 2002)

slide6

6

HYPOTHESES

1: Mucosal immunization of naïve cattle with recombinant intimin induces a more robust adaptive immune response at the recto-anal junction than subcutaneous immunization

2: An induced adaptive immune response to recombinant E. coli O157:H7 proteins is associated with decreased colonization

trial setup

7

Trial Setup
  • Trials 1, 2 and 3
  • 3 animals per group
    • Trial 1: Cholera toxin B subunits (rectal) and Freund’s (SQ)
    • Trial 2: TLR 7/8 agonist (rectal and SQ)
    • Trial 3: TLR 4 agonist (rectal and SQ)
      • Immunized weeks 0, 3, 6
cellular responses

8

cellular responses

Systemic PBMC Responses

Local MRLN Responses

trial 4

9

Trial 4
  • Is the MRNL response targeted?
    • TLR 7/8 agonist
    • All get SQ immunization week 0
    • Immunized again weeks 8 and 11
    • All SQ immunizations on same side
      • Evaluate MRLNs as well and prescapular LNs
serum antibody responses

13

Serum Antibody responses
  • All 4 trials:
    • Significant increases in titers to INT
    • Significant increases in titers to OVA in SQ groups
      • Variable responses to OVA in rectal groups
  • In trial 1 and 4:
    • Titers in SQ groups significantly increased compared to rectal groups
slide14

14

HYPOTHESES

1: Mucosal immunization of naïve cattle with recombinant intimin induces a more robust adaptive immune response at the recto-anal junction than subcutaneous immunization

(reject)

2: An induced adaptive immune response to recombinant E. coli O157:H7 proteins is associated with decreased colonization

challenge trials

15

Challenge Trials

Trials 1 and 2

Trials 3 and 4

Trial 3

10 animals per group

Previous oral or rectal exposure

Oral or rectal challenge

Trial 4

Oral group from trial 3

Rectal challenge

  • 6 animals per group
    • Immunized or sham
    • 4(trial 1) or 3 (trial 2) doses
    • Challenged
      • Rectal (trial 1)
      • Oral (trial 2)

Colonization levels followed for 4-7 weeks

Evaluated PBMC and serum antibody responses

serum antibody responses1

18

Serum Antibody Responses
  • In trials 1 and 2:
    • All animals had significant increases in titers to all proteins
      • No change 2 weeks post-challenge
  • In trials 3 and 4
    • Variable, low responses to all proteins
    • Tended to be higher in trial 4
  • In all trials:
    • Did not correlate with colonization duration
challenge conclusions

20

Challenge Conclusions
  • Immunization and experimental exposure induced lymphoproliferative responses
  • Immunization induced significant antibody responses
  • No significant increase in responses after challenge
  • Neither lymphoproliferative nor serum antibody responses conferred protection against colonization
overall summary

21

Overall Summary
  • Mucosal immunization does not induce a more robust regional immune response compared to SQ immunization
    • Regional responses overall more robust than systemic and are targeted in SQ immunization
  • Induced immune responses are not protective against challenge
thank you

22

Thank you!

Tovah Kerr

Susan Smart

Emma Karel

Fred Loaiza

Lonnie Austin

Kevin Lahmers

Tim Baszler

Tom Besser

Wendy Brown

Doug Call

Esther Trueblood

WADDL Pathologists and residents

VMP Faculty and staff

Graduate Students

Officemates

Friends

Family

Alex Beck

Andrea Hayles

Eric Sutten

Kathleen Sutten

Allison Vilander

Claire Miller

Carolyn Bohach

HaiqingSheng

Claudia Deobald

elisa
ELISA

Negative control

Samples

1:10

1:20

Positive if > average + 2 SD

1:1280

Titer is last positive dilution