Mimotopes: realization of an unlikely concept

Theoretically it seems highly unlikely that relatively small peptides could mimic functionally discontinuous epitopes of antigens. Nevertheless various recent reports show this to be the case. Peptide mimics of protein‐, polysaccharide‐ and DNA‐epitopes have been shown to be able to replace the native epitope. Moreover, some of them are able to induce, when used in a vaccine, antibodies with the same activity as that of the antibody used as a template. These mimics, called mimotopes, can be used in vaccines and diagnostics and can be developed more or less systematically using solely antibodies and random, semi‐random and dedicated peptide arrays or libraries. Furthermore, the mimotope concept which seems to have proven itself for antibody and antigen interaction can be applied equally well to many receptor ligand interactions and thus may form a new generic approach to the development of drugs. Copyright © 2000 John Wiley & Sons, Ltd.

[1]  A. Fauci,et al.  Selection of HIV-specific immunogenic epitopes by screening random peptide libraries with HIV-1-positive sera. , 1999, Journal of immunology.

[2]  W. Huse,et al.  Use of a Peptide Mimotope to Guide the Humanization of MRK-16, an Anti-P-glycoprotein Monoclonal Antibody* , 1999, The Journal of Biological Chemistry.

[3]  S. Miescher,et al.  Mimotope and Anti–Idiotypic Vaccines to Induce an Anti–IgE Response , 1999, International Archives of Allergy and Immunology.

[4]  R. Meloen,et al.  Small peptides induce antibodies with a sequence and structural requirement for binding antigen comparable to antibodies raised against the native protein. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Meola,et al.  Recognition by human sera and immunogenicity of HBsAg mimotopes selected from an M13 phage display library. , 1994, Gene.

[6]  S J Rodda,et al.  A priori delineation of a peptide which mimics a discontinuous antigenic determinant. , 1986, Molecular immunology.

[7]  R. Poljak,et al.  Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution , 1986, Science.

[8]  J. Letesson,et al.  Antigenic properties of peptidic mimics for epitopes of the lipopolysaccharide from Brucella. , 1999, Journal of molecular biology.

[9]  W. Schaaper,et al.  Screening of a Small Set of Random Peptides: A New Strategy to Identify Synthetic Peptides that Mimic Epitopes , 1997 .

[10]  M. Rowley,et al.  Mimotopes identified by phage display for the monoclonal antibody CII-C1 to type II collagen. , 1998, Journal of autoimmunity.

[11]  R. Barrett,et al.  Peptides on phage: a vast library of peptides for identifying ligands. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Jaap M Middeldorp,et al.  Localization and diagnostic application of immunodominant domains of the BFRF3-encoded Epstein-Barr virus capsid protein. , 1994, The Journal of infectious diseases.

[13]  R. Meloen,et al.  Synthetic peptide vaccines: success at last. , 1995, Vaccine.

[14]  R. Hoess,et al.  Constrained peptide libraries as a tool for finding mimotopes. , 1994, Gene.

[15]  A. Murray,et al.  Purification of monoclonal antibodies by epitope and mimotope affinity chromatography. , 1997, Journal of chromatography. A.

[16]  S. Pincus,et al.  Peptides that mimic the group B streptococcal type III capsular polysaccharide antigen. , 1998, Journal of immunology.

[17]  R. Poljak,et al.  X-ray diffraction studies of an anti-azophenylarsonate antibody and of an antigen-antibody complex. , 1985, Annales de l'Institut Pasteur. Immunologie.

[18]  I. Pastan,et al.  Identification of a peptide which binds to the carbohydrate-specific monoclonal antibody B3. , 1993, Gene.

[19]  M. Blaszczyk-Thurin,et al.  Vaccination with carbohydrate peptide mimotopes promotes anti-tumor responses , 1999, Nature Biotechnology.

[20]  Enrico A. Stura,et al.  Functional Mimicry of a Protein Hormone by a Peptide Agonist: The EPO Receptor Complex at 2.8 Å , 1996, Science.

[21]  K. Tsuneyama,et al.  Random phage mimotopes recognized by monoclonal antibodies against the pyruvate dehydrogenase complex-E2 (PDC-E2). , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Otlewski,et al.  A reinvestigation of a synthetic peptide (TrPepz) designed to mimic trypsin. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. Nicosia,et al.  Identification of HCV Core Mimotopes: Improved Methods for the Selection and Use of Disease-Related Phage-Displayed Peptides , 1997, Biological chemistry.

[24]  S. Pierce,et al.  Design and immunological properties of topographic immunogenic determinants of a protein antigen (LDH-C4) as vaccines. , 1992, The Journal of biological chemistry.

[25]  M. V. Regenmortel,et al.  From absolute to exquisite specificity. Reflections on the fuzzy nature of species, specificity and antigenic sites , 1998 .

[26]  M. V. Regenmortel,et al.  Mimotopes, continuous paratopes and hydropathic complementarity : Novel approximations in the description of immunochemical specificity , 1998 .

[27]  M. Steward,et al.  A mimotope from a solid-phase peptide library induces a measles virus-neutralizing and protective antibody response , 1995, Journal of virology.

[28]  J. Langeveld,et al.  Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie , 1996, Journal of clinical microbiology.

[29]  R. Meloen,et al.  Epitope analysis of glycoprotein I of pseudorabies virus. , 1990, The Journal of general virology.

[30]  E. Katchalski‐Katzir,et al.  Identification of a hexapeptide that mimics a conformation-dependent binding site of acetylcholine receptor by use of a phage-epitope library. , 1993 .

[31]  A. Meola,et al.  Derivation of vaccines from mimotopes. Immunologic properties of human hepatitis B virus surface antigen mimotopes displayed on filamentous phage. , 1995, Journal of immunology.

[32]  D. Margulies,et al.  Peptide libraries define the fine specificity of anti-polysaccharide antibodies to Cryptococcus neoformans. , 1996, Journal of molecular biology.

[33]  Peter W. Latham,et al.  Therapeutic peptides revisited , 1999, Nature Biotechnology.

[34]  J. Devlin,et al.  Random peptide libraries: a source of specific protein binding molecules. , 1990, Science.

[35]  W G Laver,et al.  Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex. , 1992, Journal of molecular biology.

[36]  A. Meola,et al.  Immunogenicity of filamentous phage displaying peptide mimotopes after oral administration. , 1997, Vaccine.

[37]  R. Meloen,et al.  Effects of Monoclonal Antibodies to Specific Epitopes of Rat Interleukin‐1 Beta (IL‐Iβ) on IL‐1β‐Induced ACTH, Corticosterone and IL‐6 Responses in Rats , 1995 .

[38]  R. Boshuizen,et al.  Plant–derived vaccine protects target animals against a viral disease , 1997, Nature Biotechnology.

[39]  B. Strandbygaard,et al.  Full protection in mink against mink enteritis virus with new generation canine parvovirus vaccines based on synthetic peptide or recombinant protein. , 1995, Vaccine.

[40]  P. Lachmann,et al.  C6 epitope expression by an unrelated antisense cDNA clone: an inadvertent surface-simulation mimotope , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[41]  D. Chargelegue,et al.  A Peptide Mimic of a Protective Epitope of Respiratory Syncytial Virus Selected from a Combinatorial Library Induces Virus-Neutralizing Antibodies and Reduces Viral Load In Vivo , 1998, Journal of Virology.

[42]  A. Folgori,et al.  Induction of anti‐carbohydrate antibodies by phage library‐selected peptide mimics , 1997, European journal of immunology.

[43]  D. Corey,et al.  Cyclic peptides as proteases: a reevaluation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[44]  A. Meola,et al.  Selection of antigenic and immunogenic mimics of hepatitis C virus using sera from patients. , 1996, Journal of immunology.

[45]  H. M. Geysen,et al.  Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[46]  D. Chargelegue,et al.  Synergistic effect of immunization with a peptide cocktail inducing antibody, helper and cytotoxic T-cell responses on protection against respiratory syncytial virus. , 1999, The Journal of general virology.

[47]  T. Kieber‐Emmons,et al.  Peptide mimicry of the meningococcal group C capsular polysaccharide. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[48]  J. N. Varghese,et al.  Three-dimensional structure of a complex of antibody with influenza virus neuraminidase , 1987, Nature.

[49]  P G Schultz,et al.  Peptide ligands for a sugar-binding protein isolated from a random peptide library. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[50]  T. Kieber‐Emmons,et al.  Antigenic and immunological mimicry of peptide mimotopes of Lewis carbohydrate antigens. , 1998, Molecular immunology.

[51]  B. Stadler,et al.  Allergen mimotopes in food enhance type I allergic reactions in mice , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  M. Smits,et al.  Preclinical test for prion diseases , 1996, Nature.

[53]  Smith Ja,et al.  A proposal for the nomenclature of antigenic sites in peptides and proteins. , 1978 .

[54]  F. Gebauer,et al.  Isolation of sequences from a random-sequence expression library that mimic viral epitopes , 1992, Journal of Immunological Methods.

[55]  D. Chargelegue,et al.  Peptide mimics of a conformationally constrained protective epitopes of respiratory syncytial virus fusion protein. , 1997, Immunology letters.

[56]  Richard A. Houghten,et al.  Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence , 1982, Nature.

[57]  M. Atassi,et al.  Design of peptide enzymes (pepzymes): surface-simulation synthetic peptides that mimic the chymotrypsin and trypsin active sites exhibit the activity and specificity of the respective enzyme. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[58]  H. Fukuda,et al.  Identification of peptides mimicking the antigenicity and immunogenicity of conformational epitopes on Japanese encephalitis virus protein using synthetic peptide libraries. , 1996, Journal of virological methods.

[59]  C. Partidos,et al.  Definition of the primary structure of hepatitis B virus (HBV) pre-S hepatocyte binding domain using random peptide libraries. , 1997, Virology.

[60]  B C Finzel,et al.  Three-dimensional structure of an antibody-antigen complex. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[61]  R. Meloen,et al.  Synthetic peptides for diagnostic use. , 1997, The Veterinary quarterly.

[62]  J. Scott,et al.  Searching for peptide ligands with an epitope library. , 1990, Science.

[63]  Epitope-specific antibody response to IgE by mimotope immunization. , 1998, Journal of immunology.

[64]  J. Manning.  Life cycle patterns and their genetic control: An attempt to reconcile evolutionary and mechanistic speculation , 1976, Acta biotheoretica.