Delineation of a neutralizing subregion within the immunodominant epitope (GH loop) of foot-and-mouth disease virus VP1 which does not contain the RGD motif
Identifieur interne : 000231 ( France/Analysis ); précédent : 000230; suivant : 000232Delineation of a neutralizing subregion within the immunodominant epitope (GH loop) of foot-and-mouth disease virus VP1 which does not contain the RGD motif
Auteurs : Fred Brown [États-Unis] ; Nadia Benkirane [France] ; David Limal [France] ; Hubert Halimi [France] ; John F. E Newman [États-Unis] ; Marc H. V Van Regenmortel [France] ; Jean-Paul Briand [France] ; Sylviane Muller [France]Source :
- Vaccine [ 0264-410X ] ; 1999.
English descriptors
Abstract
The major immunogenic site of foot-and-mouth disease virus (FMDV) is contained in a disordered loop comprising residues 134–158 of capsid protein VP1, located on the surface of the viral particle. Peptides corresponding to this sequence generally elicit protective levels of neutralizing antibodies in guinea pigs. In some instances, however, the level of neutralizing antibodies is low although the level of antibodies against the peptide, determined by ELISA, is as high as that in the sera with high neutralizing antibody titres. In an attempt to ascertain the reason for this difference, we have synthesized on a cellulose membrane 10 overlapping decapeptides, offset by one residue, covering the segment 141–159 of VP1 of two viruses belonging to serotypes A12 and O1, and tested them with guinea pig antisera raised against peptide 141–159, VP1 and FMDV particles (SPOTscan method). With type A, some peptides which were strongly positive with highly neutralizing antisera did not include the RGD triplet located at residues 145–147. In contrast, antisera with low neutralization titres reacted only with decapeptides which included the RGD motif. Moreover, peptide 147–156 coupled to keyhole limpet haemocyanin, but not peptide 141–149 coupled to the same carrier, elicited high levels of neutralizing antibodies in guinea pigs. In the case of serotype O, highly neutralizing antisera to virus reacted in ELISA with peptides 141–150 (containing the RGD motif) and 135–144 (located upstream from the RGD motif). The results suggest that the RGD triplet is not an indispensable constituent of peptides able to elicit a neutralizing antibody response against the virus.
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DOI: 10.1016/S0264-410X(99)00169-3
Affiliations:
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Peptides corresponding to this sequence generally elicit protective levels of neutralizing antibodies in guinea pigs. In some instances, however, the level of neutralizing antibodies is low although the level of antibodies against the peptide, determined by ELISA, is as high as that in the sera with high neutralizing antibody titres. In an attempt to ascertain the reason for this difference, we have synthesized on a cellulose membrane 10 overlapping decapeptides, offset by one residue, covering the segment 141–159 of VP1 of two viruses belonging to serotypes A12 and O1, and tested them with guinea pig antisera raised against peptide 141–159, VP1 and FMDV particles (SPOTscan method). With type A, some peptides which were strongly positive with highly neutralizing antisera did not include the RGD triplet located at residues 145–147. In contrast, antisera with low neutralization titres reacted only with decapeptides which included the RGD motif. Moreover, peptide 147–156 coupled to keyhole limpet haemocyanin, but not peptide 141–149 coupled to the same carrier, elicited high levels of neutralizing antibodies in guinea pigs. In the case of serotype O, highly neutralizing antisera to virus reacted in ELISA with peptides 141–150 (containing the RGD motif) and 135–144 (located upstream from the RGD motif). The results suggest that the RGD triplet is not an indispensable constituent of peptides able to elicit a neutralizing antibody response against the virus.</div></front></TEI><affiliations><list><country><li>France</li><li>États-Unis</li></country><region><li>Alsace</li><li>Alsace-Champagne-Ardenne-Lorraine</li><li>État de New York</li></region><settlement><li>Strasbourg</li></settlement></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Brown, Fred" sort="Brown, Fred" uniqKey="Brown F" first="Fred" last="Brown">Fred Brown</name></region><name sortKey="Newman, John F E" sort="Newman, John F E" uniqKey="Newman J" first="John F. E" last="Newman">John F. 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