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.
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.
targets of the planned research and development would be:
investigate the kinetics of induction of protection, with special
emphasis on rapid induction of early protection;
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;
characterise the effector compartments within the early immune
response against FMDV following vaccination;
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
determine the applicability of tools such as synthetic peptides
and monoclonal antibodies to the identification of effective
immune responses early after vaccination;
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;
compare the relative roles of the effector responses involved
early, in comparison to late after vaccination.
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.
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.
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
antibodies. A large panel of MAb to FMDV capsid proteins and
porcine leukocyte markers has been developed.
Epitopic constructs, bacterially expressed viral proteins
and sets of overlapping peptides corresponding to the ORF of FMDV
types C and O, have been generated.
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.
An RT-PCR assay is available for the detection of FMDV RNA
and those of other swine vesicular viruses.
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.
population analyses. No significant antigenic changes have
been observed in the leukocyte populations following vaccination.
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.
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.
haplotyping. Characterisation of SLA types in the animals
being employed in the various vaccination experiments has begun.
de investigación en Sanidad Animal
Valdeolmos - Madrid
+34 91 620 23 00
+34 91 620 22 47
- Evert J. HENSEN
Faculty of Veterinary Medicine
University of Utrecht
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
NL-B200 AB Lelystad
Tel.: +31 32 023 86 81
Fax: +31 32 023 86 68
- Birte KRISTENSEN
The Royal Veterinary and Agricultural University
Tel.: +45 35 28 27 38
Fax: +45 35 28 27 42
- Kenneth MC CULLOUGH
Institut fuer Viruskrankheiten und Immunprophylaxe Forschungsanstalt
des Bundesamtes Fuerveterinärwesen
Tel.: +41 31 848 93 61
Fax: +41 31 848 92 22
- Paul BARNETT
Institute for Animal Health
Ash Road, Pirbright
Tel.: +44 1483 23 24 41
Fax: +44 1483 23 24 48
- Armin SAALMUELLER
Bundesforschungsanstalt fuer Viruskrankheiten der Tiere
Paul-Ehrlich Str. 28
Tel.: +49 70 719 672 56
Fax: +49 70 719 673 03
- Esteban DOMINGO
Consejo Superior de Investigaciones Cientificas
Tel.: +34 91 397 84 85
Fax: +34 91 397 47 99