Single Domain Camelid Antibodies that Neutralize Negative Strand Viruses

Abstract

Recombinant antibodies (Abs) are widely regarded as one of the main, if not the most promising tools against cancer and auto-immune, inflammatory, neurodegenerative and infectious diseases (Stiehm et al., 2008). Conventional antibodies are complex molecules consisting of pairs of heavy and light chains, whose N-terminal domain is more variable than the rest of the protein sequence. The antibody heavy chain usually consists of three constant domains (CH1, CH2 and CH3) and a variable domain (VH). The light chain has only two domains, the constant light (CL) and the variable light (VL). Important Glycosylations on the CH2 domain are necessary for antibody effector functions, such as Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement–Dependent Cytolysis (CDC), and for regulating antibody half time in serum (Fig. 1, A). Antigen-binding is determined by the three hypervariable Complementary Determining Regions (CDR1, CDR2 and CDR3) present in both the VH and VL domains. These regions are located in juxtaposed loops, creating a continuous surface of ~ 1000 A2 that specifically binds to the epitope in an antigen. Although all CDRs can potentially make contact with the antigen, CDR3 contacts with the epitope are generally more extensive. The structural diversity of the antigen-binding sites of a conventional antibody depends on the size of the CDR3 in the VH and the conjunction with the VL at different angles and distances. These are grouped in three different classes, according to the size and type of antigen: cavities (fitting haptens), grooves (fitting peptides) and planar sites (fitting surface patches of proteins) (Johnson et al., 2010).