Confronting the degeneracy of convergent combinatorial immunogens, or 'mixotopes', with the specificity of recognition of the target sequences.
Immunization by convergent combinatorial peptide libraries, or 'mixotopes' represents an interesting approach for inducing broadly cross-reactive immune response to hypervariable pathogens. The authors have immunized rabbits with a series of eight HIV-1 V3-loop derived constructs of increasing complexity, and analysed the reactivity of the corresponding antisera towards a set of V3-related peptides. Results were surprisingly homogeneous. Mixotopes containing as many as several billion closely related combinatorial sequences were immunogenic, and able to induce V3-specific antibodies. These results suggest that serological cross-reactivity depends on the sequential similarity of the antigen with the parent immunogen. Such 'mixotopes' could represent a useful approach to vaccination against hypervariable pathogens.
Gras-Masse
H
H
Faculté de Pharmacie-URA CNRS 1309, Institut Pasteur de Lille, France. helene.gras@pasteur-lille.fr
Boutillon
C
C
Diesis
E
E
Deprez
B
B
Tartar
A
A
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011817:Rabbits
D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D007106:Immune Sera; D010446:Peptide Fragments