Humanization strategies for an anti-idiotypic antibody mimicking HIV-1 gp41

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Abstract

Anti-idiotypic antibodies could represent an alternative vaccination approach in human therapy. The anti-idiotypic antibody Ab2/3H6 was generated in mouse and is directed against the human monoclonal antibody 2F5, which broadly and potently neutralizes primary HIV-1 isolates. Ab2/3H6 is able to mimic the antigen recognition site of 2F5 making it a putative candidate for HIV-1 vaccine purposes. In order to reduce immunogenicity of therapeutic proteins, humanization methods have been developed. The mouse variable regions of Ab2/3H6 were subjected to three different humanization approaches, namely resurfacing, complementarity determining region (CDR)-grafting and superhumanization. Four different humanized Ab2/3H6 variants were characterized for their binding affinity to 2F5 in comparison to the chimeric Ab2/3H6. The resurfaced and the 'conservative' CDR-grafted variants showed similar binding properties to 2F5 when compared to the chimeric version, while the 'aggressive' CDR-grafted antibody showed reduced affinity and the superhumanized type lost its binding ability. In this study, we developed humanized Ab2/3H6 variants that retained the same affinity as the parental antibody, and are therefore of potential interest for future clinical trails. © The Author 2010. Published by Oxford University Press. All rights reserved.

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Mader, A., & Kunert, R. (2010). Humanization strategies for an anti-idiotypic antibody mimicking HIV-1 gp41. Protein Engineering, Design and Selection, 23(12), 947–954. https://doi.org/10.1093/protein/gzq092

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