Immunogenicity of T epitope-containing cyclic peptides. Increasing neutralizing antibody responses by introducing fine chemical changes.
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.
Léonetti
M
M
Département d'Ingéniérie et d'Etudes des Protéines (DIEP), Centre d'Etudes de Saclay, Gif-Sur-Yvette, France.
Cotton
J
J
Leroy
S
S
Mourier
G
G
Ménez
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity; D000992:Antitoxins / Q000276:immunology; D001667:Binding, Competitive; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D000992:Antitoxins; D000939:Epitopes; D010456:Peptides, Cyclic; C094442:cyclic peptide 24-41C