Comparison of antibodies and nanobodies

Antibodies

Conventional antibodies are composed of two identical heavy and two identical light chains, for a total size of approximately 150 kDa. Each heavy chain contains three constant domains (CH1 to CH3) and one variable domain (VH), and each light chain is composed of one constant (CL) and one variable domain (VL).

Structurally, conventional antibodies can be divided into the constant fragment (Fc) and the antigen-binding fragment (Fab). The combination of the VH and the VL domains forms the variable fragment, which is involved in antigen recognition, notably through their complementarity determining regions (CDRs) loops. The recombination of the VH and VL from an antibody is referred to as single-chain variable fragment (ScFv). ​

Antibody domain structure

Nanobodies (aka VHHs)

Camelids have the particularity of displaying another type of antibody, composed of only two identical heavy chains, each including two constant domains (CH1 and CH2) and one variable domain (VH). The single VH is able to recognize the antigen specifically and with high affinity, with its 3 CDR loops being responsible for binding. Nanobodies are the engineered variable domain from heavy chain-only antibodies

Llama and nanobody schematic

IgG Fv region compared with Nanobody (VHH)

Comparison of antibody Fab and nanobody