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Background The interaction of gp120 with CD4 is the first step of HIV cycle. It is the pivotal event allowing the entry of HIV into CD4+ cells. gp120 is the main target for neutralizing antibodies (nAb) but most of its accessible epitopes are highly variable and thus, HIV can bypass these nAbs. Single domain antibodies (sdAb) derived from llama antibodies bind their antigen without requiring variable domains pairing. They are able to bind unconventional epitopes, like those present in protein cavities. Their small size (13 kDa) allows them to accede to very narrow space, such as the space between virus and cell membranes during infection. SdAbs are highly stable, easy to clone and produce in large amounts.

Straightforward selection of broadly neutralizing single-domain antibodies targeting the conserved CD4 and co-receptor binding sites of HIV-1 gp120