Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics

Armelle Phalipon, Antonella Folgori, Josette Arondel, Giuseppe Sgaramella, Paola Fortugno, Riccardo Cortese, Philippe J. Sansonetti, Franco Felici

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

One of the prerequisites for the development of polysaccharide subunit vaccines is the induction of an efficient immune response to carbohydrate antigens like lipopolysaccharide (LPS) or capsular polysaccharide antigens of pathogens. In an attempt to overcome the problems that arise from the T-independent immune response induced by such antigens, selecting peptide sequences that mimic protective carbohydrate epitopes has been proposed. In this study, we investigate a new selection strategy for immunogenic peptide mimics using the phage-displayed peptide library technology. Two monoclonal antibodies (mAb) of the A isotype (mIgA), mIgA C5 and mIgA I3, specific for the O-antigen (O-Ag) part of the human pathogen Shigella flexneri serotype 5a LPS and protective against homologous infection were used to screen two phage-displayed nonapeptide libraries in pVIII. Using mIgA C5, 13 different specific clones were selected, and 6 using mIgA 13; 5 of the latter also interacted in enzyme-linked immunosorbent assay with the first mAb. All of the 19 clones selected were separately used to immunize mice, but only 2 of them, p100c (mIgA I3-specific) and p115 (interacting with both mIgA) were able to induce anti-O-Ag antibodies. The immune response was specific for the O-Ag of the S. flexneri serotype 5a, and also selectively recognized the corresponding bacterial strain. The amino acid sequences of p100c and p115 immunogenic peptide mimics were YKPLGALTH (flanked by two Cys residues) and KVPPWARTA, respectively. These results are the first example of immunogenic mimicry of carbohydrates by phage-displayed peptides, and indicate a new strategy of selection of immunogens for the development of anti-polysaccharide vaccines.

Original languageEnglish
Pages (from-to)2620-2625
Number of pages6
JournalEuropean Journal of Immunology
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 1997

Fingerprint

Peptide Library
O Antigens
Bacteriophages
Anti-Idiotypic Antibodies
Carbohydrates
Polysaccharides
Shigella flexneri
Peptides
Antigens
Lipopolysaccharides
Clone Cells
Monoclonal Antibodies
Subunit Vaccines
Libraries
Epitopes
Amino Acid Sequence
Vaccines
Enzyme-Linked Immunosorbent Assay
Technology
Antibodies

Keywords

  • Antibody
  • Carbohydrate
  • Mimotope
  • Peptide
  • Phage display

ASJC Scopus subject areas

  • Immunology

Cite this

Phalipon, A., Folgori, A., Arondel, J., Sgaramella, G., Fortugno, P., Cortese, R., ... Felici, F. (1997). Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics. European Journal of Immunology, 27(10), 2620-2625. https://doi.org/10.1002/eji.1830271022

Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics. / Phalipon, Armelle; Folgori, Antonella; Arondel, Josette; Sgaramella, Giuseppe; Fortugno, Paola; Cortese, Riccardo; Sansonetti, Philippe J.; Felici, Franco.

In: European Journal of Immunology, Vol. 27, No. 10, 10.1997, p. 2620-2625.

Research output: Contribution to journalArticle

Phalipon, A, Folgori, A, Arondel, J, Sgaramella, G, Fortugno, P, Cortese, R, Sansonetti, PJ & Felici, F 1997, 'Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics', European Journal of Immunology, vol. 27, no. 10, pp. 2620-2625. https://doi.org/10.1002/eji.1830271022
Phalipon A, Folgori A, Arondel J, Sgaramella G, Fortugno P, Cortese R et al. Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics. European Journal of Immunology. 1997 Oct;27(10):2620-2625. https://doi.org/10.1002/eji.1830271022
Phalipon, Armelle ; Folgori, Antonella ; Arondel, Josette ; Sgaramella, Giuseppe ; Fortugno, Paola ; Cortese, Riccardo ; Sansonetti, Philippe J. ; Felici, Franco. / Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics. In: European Journal of Immunology. 1997 ; Vol. 27, No. 10. pp. 2620-2625.
@article{a5660820c7a64ae2af70977bf43b8b7a,
title = "Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics",
abstract = "One of the prerequisites for the development of polysaccharide subunit vaccines is the induction of an efficient immune response to carbohydrate antigens like lipopolysaccharide (LPS) or capsular polysaccharide antigens of pathogens. In an attempt to overcome the problems that arise from the T-independent immune response induced by such antigens, selecting peptide sequences that mimic protective carbohydrate epitopes has been proposed. In this study, we investigate a new selection strategy for immunogenic peptide mimics using the phage-displayed peptide library technology. Two monoclonal antibodies (mAb) of the A isotype (mIgA), mIgA C5 and mIgA I3, specific for the O-antigen (O-Ag) part of the human pathogen Shigella flexneri serotype 5a LPS and protective against homologous infection were used to screen two phage-displayed nonapeptide libraries in pVIII. Using mIgA C5, 13 different specific clones were selected, and 6 using mIgA 13; 5 of the latter also interacted in enzyme-linked immunosorbent assay with the first mAb. All of the 19 clones selected were separately used to immunize mice, but only 2 of them, p100c (mIgA I3-specific) and p115 (interacting with both mIgA) were able to induce anti-O-Ag antibodies. The immune response was specific for the O-Ag of the S. flexneri serotype 5a, and also selectively recognized the corresponding bacterial strain. The amino acid sequences of p100c and p115 immunogenic peptide mimics were YKPLGALTH (flanked by two Cys residues) and KVPPWARTA, respectively. These results are the first example of immunogenic mimicry of carbohydrates by phage-displayed peptides, and indicate a new strategy of selection of immunogens for the development of anti-polysaccharide vaccines.",
keywords = "Antibody, Carbohydrate, Mimotope, Peptide, Phage display",
author = "Armelle Phalipon and Antonella Folgori and Josette Arondel and Giuseppe Sgaramella and Paola Fortugno and Riccardo Cortese and Sansonetti, {Philippe J.} and Franco Felici",
year = "1997",
month = "10",
doi = "10.1002/eji.1830271022",
language = "English",
volume = "27",
pages = "2620--2625",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "wiley",
number = "10",

}

TY - JOUR

T1 - Induction of anti-carbohydrate antibodies by phage library-selected peptide mimics

AU - Phalipon, Armelle

AU - Folgori, Antonella

AU - Arondel, Josette

AU - Sgaramella, Giuseppe

AU - Fortugno, Paola

AU - Cortese, Riccardo

AU - Sansonetti, Philippe J.

AU - Felici, Franco

PY - 1997/10

Y1 - 1997/10

N2 - One of the prerequisites for the development of polysaccharide subunit vaccines is the induction of an efficient immune response to carbohydrate antigens like lipopolysaccharide (LPS) or capsular polysaccharide antigens of pathogens. In an attempt to overcome the problems that arise from the T-independent immune response induced by such antigens, selecting peptide sequences that mimic protective carbohydrate epitopes has been proposed. In this study, we investigate a new selection strategy for immunogenic peptide mimics using the phage-displayed peptide library technology. Two monoclonal antibodies (mAb) of the A isotype (mIgA), mIgA C5 and mIgA I3, specific for the O-antigen (O-Ag) part of the human pathogen Shigella flexneri serotype 5a LPS and protective against homologous infection were used to screen two phage-displayed nonapeptide libraries in pVIII. Using mIgA C5, 13 different specific clones were selected, and 6 using mIgA 13; 5 of the latter also interacted in enzyme-linked immunosorbent assay with the first mAb. All of the 19 clones selected were separately used to immunize mice, but only 2 of them, p100c (mIgA I3-specific) and p115 (interacting with both mIgA) were able to induce anti-O-Ag antibodies. The immune response was specific for the O-Ag of the S. flexneri serotype 5a, and also selectively recognized the corresponding bacterial strain. The amino acid sequences of p100c and p115 immunogenic peptide mimics were YKPLGALTH (flanked by two Cys residues) and KVPPWARTA, respectively. These results are the first example of immunogenic mimicry of carbohydrates by phage-displayed peptides, and indicate a new strategy of selection of immunogens for the development of anti-polysaccharide vaccines.

AB - One of the prerequisites for the development of polysaccharide subunit vaccines is the induction of an efficient immune response to carbohydrate antigens like lipopolysaccharide (LPS) or capsular polysaccharide antigens of pathogens. In an attempt to overcome the problems that arise from the T-independent immune response induced by such antigens, selecting peptide sequences that mimic protective carbohydrate epitopes has been proposed. In this study, we investigate a new selection strategy for immunogenic peptide mimics using the phage-displayed peptide library technology. Two monoclonal antibodies (mAb) of the A isotype (mIgA), mIgA C5 and mIgA I3, specific for the O-antigen (O-Ag) part of the human pathogen Shigella flexneri serotype 5a LPS and protective against homologous infection were used to screen two phage-displayed nonapeptide libraries in pVIII. Using mIgA C5, 13 different specific clones were selected, and 6 using mIgA 13; 5 of the latter also interacted in enzyme-linked immunosorbent assay with the first mAb. All of the 19 clones selected were separately used to immunize mice, but only 2 of them, p100c (mIgA I3-specific) and p115 (interacting with both mIgA) were able to induce anti-O-Ag antibodies. The immune response was specific for the O-Ag of the S. flexneri serotype 5a, and also selectively recognized the corresponding bacterial strain. The amino acid sequences of p100c and p115 immunogenic peptide mimics were YKPLGALTH (flanked by two Cys residues) and KVPPWARTA, respectively. These results are the first example of immunogenic mimicry of carbohydrates by phage-displayed peptides, and indicate a new strategy of selection of immunogens for the development of anti-polysaccharide vaccines.

KW - Antibody

KW - Carbohydrate

KW - Mimotope

KW - Peptide

KW - Phage display

UR - http://www.scopus.com/inward/record.url?scp=0030716928&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030716928&partnerID=8YFLogxK

U2 - 10.1002/eji.1830271022

DO - 10.1002/eji.1830271022

M3 - Article

C2 - 9368618

AN - SCOPUS:0030716928

VL - 27

SP - 2620

EP - 2625

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 10

ER -