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WORKPACKAGES
4.4. Work package descriptions
Workpackage 4 : Impact of vaccination on virus dissemination and the carrier state
PARTICIPANTS
Partners 2footnote 2 and 3
Person-months per participant: 76footnote 2 16
Start date or starting event: Month 1 + see footnote 1 for partner 2.
OBJECTIVES
The objectives are to measure how rapidly and effectively emergency (high potency) FMD vaccines can protect susceptible cattle from direct contact virus challenge and to what extent they effect the kinetics and quantitative dynamics of virus replication and excretion, and thereby transmission.
Secondly, the experiments will allow us to look at the effect of high potency vaccines on preventing the establishment of the carrier state.
Thirdly, we will determine the transmission difference between strains with different spreading patron.
Finally, the experiments will provide a large panel of samples from vaccinated/unvaccinated and subsequently challenged animals, for development and validation of tests to distinguish infection from vaccination and virus detection assays.
Description of work:
- 4.1. Transmission experiments with FMDV O UKG 2001 (partner 2) - In the first experiment, vaccinate twenty cattle (150Kg) with a full bovine dose of serotype O Manisa oil vaccine and 21 days later simultaneously challenge by direct contact with 5 donor cattle infected with FMDV O UKG 2001. Five unvaccinated control animals will also be included with the challenge animals. Challenge animals will remain in direct contact with the vaccinated animals for 5 days. Measure serum antibody response by structural protein and non-structural protein ELISA, and virus neutralisation test before and after challenge. Various samples will also be taken before, during and after challenge including heparinised blood, probangs, saliva and/or nasal swabs to determine the level of virus replication in each of the vaccination groups, using virus isolation and quantitative RT-PCR. Animals will be monitored for protection and the absence of clinical signs for 10 days following challenge. The experiment will continue for a minimum of 21 days post challenge and samples will be taken to examine and quantify virus excretion and antibody development over the early stages of infection and particularly the acute phase. Depending on the protective effect of the vaccine, up to 12 animals will be kept on for a period of approximately 4 months to monitor long-term virus carriage and antibody development.The experiment will be repeated five times to enable the affect of two different virus payloads (minimal and ten times minimal doses) and three different vaccine/challenge intervals (21, 10 and 4 days) to be compared with statistical validity.NB: The first two experiments will be carried out independently in 2003. The next four experiments will be conducted during the first two years of this FP6 project.
- 4.2. Transmission experiments with FMDV O NET 2001 (partner 3) - Similar experiment with cows, pigs, sheep and milking-cows as point of comparison:
- Transmission study in randomly mixed vaccinated and non-vaccinated calves (O NET/2001).
- Transmission study in randomly mixed vaccinated and non-vaccinated milking cows (O NET/2001).
- Transmission study in randomly mixed vaccinated and non-vaccinated sheep (O NET/2001 and Asia-1 Turkey 2000).
- Transmission study in randomly mixed vaccinated and non-vaccinated pigs.
- Transmission study in randomly mixed vaccinated and non-vaccinated calves (alternative strain) (2x).
Deliverables:
- D.30 - Knowledge on the clinical protective effect of FMD vaccination against contact challenge in cattle, calves, sheep and pigs and on how varying dose of vaccine and vaccine/challenge interval affects this.
- D.31 - Knowledge on the effect of FMD vaccination in preventing virus replication and shedding in contact challenged cattle, calves, sheep and pigs and on how varying dose of vaccine and vaccine/challenge interval affect this.
- D.32 - Knowledge on the effect of high potency vaccination in reducing the development of the carrier state in cattle.
- D.33 - Estimation of the reproduction ratio in vaccinated calves, cows, sheep and pigs.
- D.34 - Sera and other clinical materials from vaccinated/unvaccinated and contact challenged cattle, calves, sheep and pigs for the development and validation of tests to detect infection, regardless of vaccination status.
- D.50 - Reports: Scientific publications.
Milestones and expected result:
- - Completion of first experiment partner 2 using a high potency vaccine and a 21 day vaccination/challenge interval (already completed during 2003).
- - Completion of second experiment partner 2 using a normal potency vaccine and a 21 day vaccination/challenge interval (already completed during 2003).
- M.21 - Completion of third experiment partner 2 using a high potency vaccine and a 10 day vaccination/challenge interval (month 12).
- M.22 - Completion of fourth experiment partner 2 using a normal potency vaccine and a 10 day vaccination/challenge interval (month 12).
- M.23 - Completion of transmission study in calves and milking cows partner 3 (O NET 2001) (month 12).
- M.24 - Completion of transmission study in sheep partner 3 (Asia1) (month 18).
- - Publication of transmission study in calves (partner 3) (O NET 2001) (month 18).
- M.25 - Completion of fifth experiment partner 2 using a high potency vaccine and a 4 day vaccination/challenge interval (month 24).
- M.26 - Completion of sixth experiment partner 2 using a normal potency vaccine and a 4 day vaccination/challenge interval (month 24).
- M.27 - Completion of transmission study in sheep and pigs partner 3 (O NET 2001) (month 28).
- - Publication of transmission study in milking cows partner 3 (O NET 2001) (month 36).
- M.28 - Completion of transmission study in calves partner 3 (alternative strain) (month 36 and 42).
- - Publication transmission study pigs partner 3 (O NET 2001) (month 48).
1. This project is already going ahead, funded by our own Ministry (DEFRA) in the UK (Project code SE2808). However, the DEFRA project only covers the period until three weeks after challenge. We wish to obtain additional funding to enable us to keep the animals for an extra 4 months, so that the carrier status and longer-term NSP antibody responses can be studied. Since the EU will not fund work before the start of the project, we will only be claiming for the additional costs in respect to the four experiments being conducted in 2004 and 2005.
2. Of which 18 are additional man-months needed for the EU project and not already covered by SE808.
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