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Synthetic food-and-mouth disease virus vaccine

Objectif

Foot-and-Mouth Disease Virus (FMDV), although absent in 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 o the EU production animals (bovines, pigs and sheep) are unprotected (due to the non-vaccination policy), a highly dangerous situation exists. Any FMDV infection may potentially iniate a full-blown FMDV outbreak, which ultimately may devastate EU animal production with longterm economic consequences.

To contain outbreaks only one vaccine, based on inactivated virus, is presently available. Because this vaccine depends on the production of virulent virus a need exists for alternative FMDV vaccines based on noninfectious materials since.

In the past, outbreaks have been associated with incomplete inactivation of vaccine virus. Many attempts have been made to develop completely safe alternatives. The most promising one is based on the use of synthetic peptides.

However, 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; none of them 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.

Furthermore all synthetic vaccines for FMDV are based on peptides representing a single antigenic site. Ample evidence suggests that intact FMDV contains multiple discrete neutralizinq antiqenic 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.

The 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.

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INSTITUTE VOR ANIMAL SCIENCE AND HEALTH
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