CONFRONTING THE DEGENERACY OF CONVERGENT COMBINATORIAL IMMUMOGENS, ORMIXOTOPES, WITH THE SPECIFICITY OF RECOGNITION OF THE TARGET SEQUENCES

Immunization by convergent combinatorial peptide libraries, or 'mixoto pes' represents an interesting approach for inducing broadly cross-rea ctive immune response to hypervariable pathogens. The authors have imm unized rabbits with a series of eight HIV-1 V3-loop derived constructs of increasing complexity, and analysed the reactivity of the correspo nding antisera towards a set of V3-related peptides. Results were surp risingly 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 w ith the parent immunogen. Such 'mixotopes' could represent a useful ap proach to vaccination against hypervariable pathogens. (C) 1997 Elsevi er Science Ltd.