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WORKPACKAGES
4.4. Work package descriptions
Workpackage 5 : Improved vaccine strain selection
PARTICIPANTS
Partners 1, 2, 3, 4, 5, 7 and 8
Person-months per participant: 36, 4, 10, 36, 40, 28 and 39
Start date or starting event: Month 1
OBJECTIVES
It is in the interest of the decision makers responsible for antigen banks to select vaccine strains that are as immunogenic and cross-reactive as possible. In case of an FMD outbreak with a new strain it is essential to match the vaccine strains as closely as possible to the field strains. It is therefore necessary to continuously monitor the prevailing FMD viruses. Typing is done by means of serotyping and genotyping: r-value determination, nucleotide sequencing and antigen profiling. What is available at present gives only a very crude assessment and its reliability is open to question. There is a pressing need to improve and standardise the available methods for antigenic comparison between vaccine strains and field viruses. The objectives are the following:
- Provide definite information on the degree of cross-protection between key vaccine and field virus strains.
- Improvement and standardisation of in vitro vaccine/virus comparisons. Determination of the relevance and of the relation between r-value, antigen profiling and genotyping.
- Development of an alternative method for vaccine potency test to replace the current challenge test.
- Development of MAbs profiling assays to characterise and compare the antigen structure of vaccine and field strains.
- Validation of vaccination efficiency in terms of blockage of circulation of various types of FMDV under different field conditions and different vaccination strategies.
- Improvement of methods to trace FMDV strains and in particular to resolve the dynamic of an emerging epidemic to support decisions related to emergency vaccination regimes.
Description of work:
- 5.1 Cross-protection challenge (0 - 42 months) - In 20 animal experiments cattle, sheep, goats and pigs will be vaccinated with highly potent conventional 146S vaccines and challenged with a homologous as well as one or more heterologous viruses. After challenge clinical signs and virus excretion will be determined and sera collected (partners 1, 2, 3 and 5).
- 5.2 Determination r-value (3 - 48 months):
- 5.2.1 Determination of r-values by ELISA and VNT and relation to genotyping and antigen profiling (partners 1 and 2).
- 5.2.2 Developing a competition ELISA for r-value determination (partner 2).
- 5.3 Antigen profiling - Development and characterisation of MAbs panels against vaccine strains and emerging field isolates (partner 7 and 8) (3 - 48 months).
- 5.4 Sequencing of vaccine and challenge strains (3 - 48 months) - Defining the most interesting regions of the FMDV genome involved in vaccine response and/or vaccine formulation. Sequencing of FMDV vaccine strains, challenge strains and samples from vaccinated or non-vaccinated animals, exposed to infection. It will be used for monitoring the vaccine response in infected animals (partners 1 and 2).
- 5.5 Genetic and antigenetic typing by monitoring in an endemic situation (partner 4, 7 and 8) (0 - 48 months):
- 5.5.1 Longitudinal characterisation in defined areas of the genetic and antigenetic diversity of circulating FMDV strains in particular in response to vaccination programs in order to evaluate the efficacy of vaccination programs in terms of blockage of FMDV circulation.
- 5.5.2 Characterisation of the quasispecies structures of FMDV strains in order to improve methods of resolving the initial dynamic of emerging epidemics.
- 5.5.3 Serological titre determination by monitoring in a field area free from FMD and determine correlation with protection (partner 8).
Deliverables
- D.35 - Improved r-value (VNT, ELISA) for various FMD strains of epidemiological importance and data on the relation of r-value and protection against heterological challenge. The relation between r-value, antigen profiling and genotyping.
- D.36 - Data on the relation of antigen profiling and protection against heterological challenge.
- D.37 - Data on the relation of genotyping and protection against heterological challenge.
- D.38 - Samples for all assay validation and development during this project.
- D.39 - Characterised MAbs panels suited for antigen profiling and improved antigen profiling.
- D.40 - Improved sequencing for detecting and identifying FMDV genetic variants with different response to vaccines.
- D.41 - Alternative potency test.
- D.42 - Better knowledge of FMDV strain selection in endemic areas of the world and data on the ability to adapt antigen of vaccines to specific epidemiological situations.
Milestones and expected result
- M.29 - Improved of r-value, antigen profiling and genotype determination.
- M.30 - Homologous and heterologous challenge data.
- M.31 - Improved vaccine strain selection tests.
- M.32 - Identified sequences involved in vaccine response.
- M.33 - Identified and published genetic diversity of FMDV strains in Turkey and Uganda and its relation to vaccine strain selection.
- M.34 - Improved basis for decision-making in relation to emergency vaccination.
- M.35 - Reduced costs for vaccine potency test.
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