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Induction of early protection against foot and mouth disease

Contract nr: FAIR-CT97-3665
Project nr: 3665
Project type: SC
Starting date: 01/03/1998
Duration: 36 months
Total cost: 1,129,631 EUR
EC Contribution: 1,300,000 EUR
Scientific Officer: Isabel MINGUEZ-TUDELA
Research topic: Animal health

Foot-and-mouth disease (FMD) is a viral infection of cloven-hoofed animals currently endemic in Africa, Asia, the Middle East and S. America. The success of vaccination has prompted the EU to adopt a total stamping-out policy since 1991. As a consequence, a fully susceptible farm animal population prevails at present in the EU countries, potentially threatened by border countries where the disease is enzootic. The disease currently presents a constant threat to Europe, as witnessed over the last 12 months in the Balkans, with the outbreaks in Italy (1993) and Greece (1994) supporting this concern about disease re-introduction into Europe. Of particular relevance in this context is consideration of excretion rates of the virus by infected animals, which can occur before clinical diagnosis is possible. The policy for controlling outbreaks is a zonal slaughtering in the contaminated area, concomitant with a ring quarantine and surveillance around the outbreak site. If this system proves inadequate, a vaccination campaign is effected. Of particular benefit to the control measures would be an effective emergency vaccination scheme, which would ensure the rapid development of early protection.

The basic objective of the current proposal is to identify the potential for an emergency vaccination scheme wherein a rapid induction of early protection against FMD could be effected. Towards this end, it is essential to investigate the characteristics of the early immune response against FMDV, induced by vaccination, which would result in efficient and, particularly, rapid protection against the disease.

The targets of the planned research and development would be:

1) investigate the kinetics of induction of protection, with special emphasis on rapid induction of early protection;

2) determine the influence of the route of immunisation (aerosol from contact infected animal, snout inoculation, intranasal) on the outcome of the attempted vaccine-induced protection;

3) characterise the effector compartments within the early immune response against FMDV following vaccination;

4) investigate the potential for different forms of the FMDV vaccine (different vaccine formulations and different FMDV immunogens), with respect to inducing early protection with longevity of response;

5) determine the applicability of tools such as synthetic peptides and monoclonal antibodies to the identification of effective immune responses early after vaccination;

6) improve surveillance and epidemiological procedures for FMDV identification and characterisation, through the incorporation of new molecular biology approaches to the diagnosis and characterisation of FMDV field strains;

7) compare the relative roles of the effector responses involved early, in comparison to late after vaccination.

It is proposed to concentrate on the porcine response as both a model and of direct consequence to animal health. Therein, the experimental design and rational can be summarised as a study of the early immunological defences induced by FMDV vaccines, containing different forms of the immunogen and different formulations. Both the innate and specific immune responses will be identified, in terms of their efficacy in defending against FMDV, and their duration. The characterisation of the specific response will be made in terms of the epitopes recognised.

These latter analyses will help define the response developing, and in association with the innate response analyses, determine characteristics of the immune response which could be employed as determinants of an effective vaccination with respect to the induction of early protection with a minimum longevity.

Current situation/results:
Vaccinations. The systemic production of TNF, IFN and TGF was monitored in vaccinated pigs, and no single cytokine response could be found associated to the early protective immune response. FACS analysis is being used to look at any phenotypic changes in the cell populations after vaccination.
Monoclonal antibodies. A large panel of MAb to FMDV capsid proteins and porcine leukocyte markers has been developed.
Peptides. Epitopic constructs, bacterially expressed viral proteins and sets of overlapping peptides corresponding to the ORF of FMDV types C and O, have been generated.
Recombinant viruses. The P1 coding region (VP1-VP4) of type C and O have been expressed in vaccinia and adenovirus vectors. The immunogencicity of these recombinants in pigs is being assessed.
PCR. An RT-PCR assay is available for the detection of FMDV RNA and those of other swine vesicular viruses.
Cytokine tools. Porcine IL-2 and IL-6, GM-CSF and IL-1 have been cloned and express. Neutralising MAb against IL-2 and IL-1 were generated. Bioassays are available for porcine IFNs, IL-1,2, 6, 8, 10,12, TNF and TGF.
Leukocyte population analyses. No significant antigenic changes have been observed in the leukocyte populations following vaccination.
Innate immunity. An analysis of the innate response has begun. Macrophage differentiation monitoring, NK assays and functional analysis of the differentiated cells, including phagocytic and endocytic activity are being used.
Specific immunity. T cell epitopes have been identified as being recognised by the porcine immune system. One of these T cell epitopes was functional in a vaccine preparation inducing protection in cattle.
SLA haplotyping. Characterisation of SLA types in the animals being employed in the various vaccination experiments has begun.

Francisco SOBRINO
Centro de investigación en Sanidad Animal
E-28130 Valdeolmos - Madrid
Tel.: +34 91 620 23 00
Fax: +34 91 620 22 47


  • Evert J. HENSEN
    Faculty of Veterinary Medicine
    University of Utrecht
    Yalelaan 1
    NL-3508 TD Utrecht
    Tel.: +31 30 253 24 71
    Fax: +31 30 253 35 55

  • Remco R. SCHRIJVER
    DLO - Institute for Animal Science and Health
    Edelhertweg 15
    NL-B200 AB Lelystad
    Tel.: +31 32 023 86 81
    Fax: +31 32 023 86 68

    The Royal Veterinary and Agricultural University
    Bülowsvej 13
    DK-1870 Frederiksberg
    Tel.: +45 35 28 27 38
    Fax: +45 35 28 27 42

  • Kenneth MC CULLOUGH
    Institut fuer Viruskrankheiten und Immunprophylaxe Forschungsanstalt des Bundesamtes Fuerveterinärwesen
    Sensemattstrasse 293
    CH-3147 Mittelhäusern
    Tel.: +41 31 848 93 61
    Fax: +41 31 848 92 22

  • Paul BARNETT
    Institute for Animal Health
    Ash Road, Pirbright
    UK-Surrey Woking
    Tel.: +44 1483 23 24 41
    Fax: +44 1483 23 24 48

    Bundesforschungsanstalt fuer Viruskrankheiten der Tiere
    Paul-Ehrlich Str. 28
    D-72076 Tuebingen
    Tel.: +49 70 719 672 56
    Fax: +49 70 719 673 03

  • Esteban DOMINGO
    Consejo Superior de Investigaciones Cientificas
    Serrano 113
    E-28006 Madrid
    Tel.: +34 91 397 84 85
    Fax: +34 91 397 47 99

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