Structural studies on antibodies originatingfrom the VH1-69 germline reveal that several residues at the heavy chaincomplementarity determining region (HCDR) 2 unique to this germline areimportant for viral recognition. The anti-HIV antibody D5 is one example of aVH1-69 antibody. We hypothesize that a D5-based synthetic antibody library,where the VH1-69-derived HCDR2 serves as a critical anchor point, can be usedto identify novel antibodies that have unique recognition properties againstviral targets. A D5-based synthetic antibody library was constructed and wassubjected to selection against the HIV-1 gp41 antigen, 5 helix. Polyclonalphage ELISA suggests there is enhanced binding to HIV 5-helix in the thirdround population. Four unique sequences have been identified and we are in theprocess of identifying additional unique binding clones by high throughputphage ELISA. We are in the process of selecting for antibodies against otherviral targets.

Alternative scaffold for generation of synthetic antibody libraries

241st National Meeting (2011)

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