Immunogenicity of T epitope-containing cyclic peptides. Increasing neutralizing antibody responses by introducing fine chemical changes

J Immunol. 1995 Jul 1;155(1):210-8.

Abstract

We showed previously that the disulfide-containing T peptide 24-41 C from a highly structured snake toxin elicits, in a free state, Abs that neutralize the toxin, and only a turn structure commonly exists in 24-41 C and the corresponding toxin region. To tentatively increase the neutralizing capacity of antipeptide Abs, we 1) replaced Gly-40 by an aminoisobutyric moiety (24-41 Aib), 2) substituted the half cystines 24 and 41 by penicillamine moieties (24-41 Pen), and 3) introduced an amide bond between the epsilon NH2 of Lys-27 and the gamma-COOH of Glu-38 (24-41 K-E). A solution ELISA made with antitoxin Abs revealed that 24-41 Pen is more antigenic than 24-41 Aib and 24-41 C, which are more antigenic than 24-41 K-E, suggesting that the conformation of 24-41 Pen is most closely related to the corresponding region in the native toxin. The peptides 24-41 Pen, 24-41 Aib, and 24-41 C stimulate T cells from BALB/c mice, whereas 24-41 K-E has lost this property and thereby fails to elicit Abs. Finally, anti-24-41 Pen Abs are more potent at neutralizing the native toxin than anti-24-41 C Abs, which are more potent than anti-24-41 Aib Abs. The efficacy of anti-24-41 Pen Abs was similar to that of a toxin specific mAb. Therefore, introduction of appropriate constraints makes it possible to improve the neutralizing Ab response raised by a synthetic peptide. Such observations should be of interest for the design of efficient synthetic vaccines.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Antibody Formation / immunology*
  • Antibody Specificity
  • Antitoxins / immunology
  • Binding, Competitive
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Antibodies
  • Antitoxins
  • Epitopes
  • Peptides, Cyclic
  • cyclic peptide 24-41C