Disease Virus (FMDV), although absent throughout most of the EU,
is not yet eradicated. In countries neighbouring the EU it is
still endemic. Since FMDV is the most contageous virus known,
and since most of the EU production animals (bovines, pigs and
sheep) are unprotected (due to the non-vaccination policy), a
highly dangerous situation exists.
FMDV infection may potentially iniate a full-blown FMDV outbreak,
which ultimately may devastate EU animal production leading to
long-term economic consequences. To contain outbreaks only one
vaccine, based on an inactivated virus, is presently available.
Because this vaccine depends on the production of a virulent virus,
a need exists for alternative FMDV vaccines based on non-infectious
materials. In the past, outbreaks have been associated with incomplete
inactivation of the vaccine virus. Many attempts have been made
to develop completely safe alternatives. The most promising one
is based on the use of synthetic peptides.
in contrast to the classical vaccine, this synthetic vaccine only
partially protects the target animal. Numerous substantial attempts
have been made to improve the peptide vaccine; but none was fully
successful. However, recently, in the context of an EC-Bridge
project, it was shown for the first time that synthetic peptide
vaccines representing a single antigenic site can induce indeed
full protection in the target animal (parvo virus in dogs and
mink). This success directly points to an alternative approach
to design synthetic vaccines for FMDV. FMDV, which is an RNA virus,
has a much higher potential to escape immune surveillance than
parvo virus, which is a DNA virus.
all synthetic vaccines for FMDV are based on peptides representing
a single antigenic site. Ample evidence suggests that intact FMDV
contains multiple discrete neutralizing antigenic sites. Taken
together, this suggests that when additional antigenic sites are
combined with the existing one in a peptide vaccine, instead of
incomplete protection full protection will be obtained.
aim of this proposal is to reconstruct one or more of the additional
antigenic sites as small peptides or peptide-like molecules and
to combine it with the existing one (the '140-160 loop'). It is
foreseen that the most challenging part is to design peptides
or peptide-like molecules that mimic conformational or discontinuous
antigenic sites. Because this is an ambitious undertaking, groups
with state of the art expertise in the field of epitope mapping,
peptide chemistry, structure chemistry, physical chemistry, virology
and vaccinology are combined.
promising groups of peptides reactive with neutralizing monoclonal
antibodies were defined using synthetic random peptide arrays.
Although these low activity lead peptides were good antigens,
their immunogenic properties were suboptimal, as expected. Nevertheless
some of these leads were able to induce similar protection in
guinea pigs as that obtained with the existing site D construct
for serotype C. The latter construct was tested in cattle and
was found to induce neutralizing activity. Using molecular modelling,
the site D construct for serotype C was translated to type O1BFS.
This construct will be tested in protection experiments and if
successful will be a major part of the final multi epitope vaccine.
second part major part will be the "140-160" loop or
site A. The extended knowledge on this site A and the finding
that T-B cel constructs can induce neutralization in cattle will
be combined with the new experiences with cyclic constructs of
site A and C and tested in protection experiments in guinea pigs.
progress was made in the development of carrier molecules and
adjuvant-carrier constructs. Several different basic construct
have become available and the synthesis of the first fully synthetic
epitope-carrier construct is underway.
Robbert Hans MELOEN
Institute for Animal Science and Health Researchhead Office
NL-8200 AB Lelystad
Tel.: +31 320 23 81 36
Fax: +31 320 23 80 50
- William GIBBONS
University of London
29/39 Brunswick Square
UK-WCIN 1AX London
Tel.: +44 1717 53 58 84
Fax: +44 1712 78 19 39
- Ernest GIRALT
Universitat de Barcelona
Gran Via 585
Tel.: +34 934 02 12 62
Fax: +34 933 39 78 78
- Marc H.V. VAN REGENMORTEL
CNEVA - Centre National d'Etudes Vétérinaires et alimentaires - EPA
Rue du Loess 23
Tel.: +33 3 88 41 70 22
Fax: +33 3 88 61 06 80