Recombinant binder proteins

Next Biomed has developed a collection of bioengineered high-affinity polypeptides (BHAP) specific for HIV-1 p24 as well as HIV-2 p26. Next Biomed’s BHAP molecules are available in different formats, that conveniently replace monoclonal antibodies in existing diagnostic platforms. These high-affinity reagents have been rationally targeted to bind to the most invariable structural determinants in p24, which are typically formed by highly conserved, non-consecutive amino acid side chains of the capsid protein.

A good example is a recombinant BHAP recognizing a p24 structure that can be mimicked by a linear peptide. About 2500 p24 sequences belonging to diverse clades of HIV-1 in the Los Alamos National Laboratory HIV Sequence Database (http://www.hiv.lanl.gov/content/sequence/HIV/mainpage.html) correspond to 123 different variants of this peptide. When tested on a peptide array, the BHAP recognizes all of these 123 different peptides strongly and evenly.

Following the development of BHAPs with exceptionally favorable target specificities their binding strength, especially the off-rate of binding, has been improved via an extensive bioengineering scheme involving both rational and random approaches. A similar systematic approach for developing superior detection reagents can be applied to other challenging diagnostic target antigens, including additional viral proteins.