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Title: ANTIGENIC MIMICRY WITH AN ALL-D-RETRO PEPTIDE CORRESPONDING TO THE IMMUNODOMINANT LOOP OF FOOT-AND-MOUTH DISEASE VIRUS

Author
item MULLER, SYLVIANE - INST. DE BIOLOGIE, FRANCE
item BRIAND, JEAN - INST. DE BIOLOGIE, FRANCE
item BENKIRANE, NADIA - INST. DE BIOLOGIE, FRANCE
item GUICHARD, GILLES - INST. DE BIOLOGIE, FRANCE
item NEWMAN, JOHN F - FORMER PIADC EMPLOYEE
item Brown, Fred
item ROWE, A - CDC ATLANTA, GEORGIA

Submitted to: Cold Spring Harbor Press
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Retro-inverso peptides, also known as all-D-retro or retro-enantio peptides, are composed of D-amino acids assembled in the reverse order from that of the parent L-sequence. Since the orientation of the side-chains in a retro-inverso analogue is very similar to that in the parent L-peptide, this leads to a high level of antigenic cross-reactivity between the two peptides. The potential of retro-inverso peptides as synthetic vaccines has been invertigated in the case of FMD. A single inoculation of retro-inverso peptide corresponding to residues 141-159 of the VP1 protein of FMDV induced longer-lasting and higher antibody titres in immunized animals than the corresponding L-peptides. The antibodies cross-reacted strongly with virus particles and with L-peptides and conferred substantial protection in guinea-pigs challenged with the cognate virus. Retro-inverso peptides have considerable potential as synthetic vaccines, since their increased resistance to proteases may overcome one of the major drawbacks of classical L-peptide vaccines.

Technical Abstract: FMDV is composed of one molecule of single-stranded RNA encapsidated in a shell comprising 60 copies of each of three proteins, VP1, VP2, VP3 and incorporating 60 copies of internal protein VP4. A disordered loop comprising amino acids 135-158 of VP1, present on the surface of the particle, contains the major immunogenic epitope. A single inoculum of a peptide corresponding to this loop usually elicits levels of neutralizing antibodies that protect guinea pigs against a severe challenge with infectious doses of cognate virus. The peptide bond is highly vulnerable to proteolytic enzymes. We have sought to overcome this problem by replacing the standard L-peptides with pseudo-peptides or peptide mimetics that contain changes in the amide bond. This is achieved by assembling D-amino acids in reverse order with respect to original sequence. In preliminary experiments with two 19-amino acid sequences corresponding to the disordered loop of FMDV, we had shown that retro-inverso peptides cross-react with antisera raised against thr L-peptides and vice versa. We have extended this work to determine whether the antibodies produced by an all-D-retro-peptide will neutralize the virus in vitro and afford protection of in vivo.