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In the giant struggle with the long chronic HIV infection the immune system has generated unique antibodies matured to neutralize a virus which has evolved to escape them. I will describe unique features of a CD4bs (m18), and two CD4i (m12, X5) antibodies selected from immune phage libraries developed from long-term nonprogressors with high levels of broadly neutralizing antibodies. The m18 H3 shows striking similarity to the Ig CDR2-like C'C" region of the CD4 domain 1 which dominates the binding to gp120. The X5 H3 is exceptionally flexible – IgG X5 inhibits efficiently infections of cells with low surface concentrations of CCR5. M12 is the only HIV-specific antibody identified which does not express its light chain but still binds gp120 – it was engineered to a single domain antibody that neutralized isolates from different clades.

retrovirology

Cross-Reactive HIV-1 Neutralizing Human Monoclonal Antibodies with Unique Features: Structural Mimicry of CD4, Conformational Flexibility, Lack of Light Chain