Longevity of protection in cattle following vaccination with emergency FMD vaccines from the UK strategic reserve

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1 Longevity of protection in cattle following vaccination with emergency FMD vaccines from the UK strategic reserve Sarah Cox, Satya Parida, Pip Hamblin, Bartek Bankowski Veronica Carr, David Paton and Paul Barnett Institute for Animal Health, UK

2 Preliminary Conclusions Immunisation with a single shot of vaccine containing high antigen payload will protect cattle from clinical disease at 6 months and a boost may be unnecessary. Some cattle develop subclinical infection. Increasing the antigen payload 5fold did not improve the immune responses so far investigated or provide additional protection from subclinical infection.

3 Control policy change Consider emergency vaccination more readily Vaccinationtolive providing absence of infection can be demonstrated, animals would not be culled and disease free status can be regained 6 months after last vaccination Duration of response??? Boost required during prolonged outbreak??? Generally accepted for conventional, prophylactic vaccination that a second injection is required to maintain immunity at protective levels for 6 months

4 Previous work Reference Serotype Species Result Hunter, 1996 SAT Cattle Oil adjuvanted vaccine maintained high level antibody for 6 months Barnett et al., 1996 A24 Cattle Failed to demonstrate long duration of immunity with oil adjuvanted vaccine Cox et al., 2003 O, A, C Sheep, pigs Good primary response demonstrated in both species which lasted at least 6 months. Pigs protected from challenge at 7 months. Selman et al., 2006 O, A, Asia 1 Cattle, sheep, pigs Oil adjuvanted vaccine maintained high level antibody for 6 months

5 Objectives: To determine the longevity of protective immunity following a single emergency vaccination of cattle To establish whether the immune response could be further optimised by increasing the antigen payload Study Plan: Perform 4 cattle experiments over 3 years Serotypes: A, O, SAT and Asia 1 Two antigen payloads Cattle to be held 6 months at Compton before transfer to Pirbright for challenge

6 Experiment 1 Group 1: 10 cattle immunised with (field dose) A22 Iraq oil adjuvanted vaccine Group 2: 10 cattle immunised with A22 Iraq oil adjuvanted vaccine Group 3: 2 unvaccinated cattle

7 6 month period post vaccination Samples: Clotted blood; heparinised blood; saliva; nasal fluid Analyses: Neutralising antibody; total specific immunoglobulin; antibody isotypes IgM, IgG1, IgG2, and IgA against FMDV Cytokine responses (systemic levels and in vitro whole blood stimulation assays) Cellular responses (in collaboration with Immunology)

8 VNT Results pre challenge Antibody titre antigen payload Days post vaccination FMD 23 FMD 24 FMD 25 FMD 26 FMD 27 FMD 28 FMD 29 FMD 30 FMD 31 FMD 32 Antibody titre antigen payload Days post vaccination FMD 34 FMD 35 FMD 36 FMD 37 FMD 38 FMD 39 FMD 40 FMD 41 FMD 42 FMD 43

9 VNT Results pre challenge antibody titre Days post vaccination unvacc

10 T cell Proliferation assays FMD 30 Media PWM BHV1 (1:10) Mock (1:10) Antigen FMD 30 Media PWM Cells only Cells only Antigen Mean cpm Mean cpm

11 Summary of FMD specific Tcell proliferation Ref Ag Days post vaccination FMD 23 FMD 24 FMD 25 FMD 26 FMD 27 FMD 28 FMD 29 FMD 30 FMD 31 FMD 32 FMD 33 unvacc None detected; weak; strong

12 Summary of FMD specific Tcell proliferation Ref Ag Days post vaccination FMD 34 FMD 35 FMD 36 FMD 37 FMD 38 FMD 39 FMD 40 FMD 41 FMD 42 FMD 43 FMD 44 unvacc None detected; weak; strong

13 Transfer to Pirbright All cattle transferred to Pirbright Homologous challenge intradermolingual to mimic that performed in potency tests Monitored and sampled for 10 days Samples as pre challenge and also oropharyngeal fluid

14 Development of clinical FMD and viraemia Vaccinated cattle: Regardless of postvaccinal immune responses, all cattle, in both antigen payload groups, were protected from clinical FMD and no viraemia was detected. Control unvaccinated cattle: Generalisation of FMD to feet was evident from 2 and 3 days post inoculation. Viraemia was detected at 2 and 4 days post inoculation

15 Development of subclinical infection Animal Treat Oropharyngeal fluid isolation (dpc) NSAb 4fold VNT FMD < FMD <1.35 <1.35 Yes FMD25 <1.35 <1.35 <1.35 <1.35 FMD Yes Yes FMD 27 Yes FMD 28 FMD 29 FMD 30 Yes FMD 31 <1.35 < FMD 32 <1.35 Yes FMD <1.35 Yes FMD < Yes FMD <1.35 Yes FMD 37 FMD <1.35 ns Yes FMD 39 < <1.35 <1.35 FMD 40 Yes FMD 41 <1.35 FMD <1.35 Yes Yes FMD 43 x5 <1.35 <1.35 <1.35 <1.35 <1.35 FMD 33 0 < <1.35 <1.35 Yes Yes FMD <1.35 <1.35 <1.35 Yes Yes

16 Preliminary Conclusions Immunisation with a single shot of vaccine containing high antigen payload will protect cattle from clinical disease at 6 months and a boost may be unnecessary. Some cattle develop subclinical infection. Increasing the antigen payload 5fold did not improve the immune responses so far investigated or provide additional protection from subclinical infection.

17 Acknowledgements This work was supported financially by Defra, UK (SE2812) and thanks are due to the animal technicians at both Compton and Pirbright for their assistance and care of the cattle used in this study.

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