Abstract
Nanobodies or VHH (variable domains of heavy-chain only antibodies) are derived from camelid species such as llamas and camels. Nanobodies isolated and selected through phage display can neutralize a broad range of human immunodeficiency virus type 1 (HIV-1) strains. Nanobodies fit into canyons on the HIV envelope that may not be accessible to IgG (immunoglobulin G) containing both heavy and light chains, and they tend to have long CDR3 (complementarity-determining region 3) loops that further enhance recognition of otherwise cryptic epitopes. Nanobodies are readily expressed at high levels in bacteria and yeast, as well as by viral vectors, and they form relatively stable, heat-resistant molecules. Nanobodies can be linked to human Fc chains to gain immune effector functions. Bivalent and trivalent nanobodies recognizing the same or distinct epitopes on the envelope glycoproteins, gp120 and gp41, greatly increase the potency of HIV-1 neutralization. Nanobodies have potential applications for HIV-1 diagnostics, vaccine design, microbicides, immunoprophylaxis, and immunotherapy.
Highlights
Nanobodies represent the Variable regions of the Heavy chain of Heavy-chain only (VHH)immunoglobulins (Figure 1)
In this review we focus on the properties and potential applications of human immunodeficiency virus type 1 (HIV-1)-neutralizing nanobodies
This study provided proof of principal that HIV-neutralizing single chain antibodies can be elicited in camelids by experimental immunization [25]
Summary
Nanobodies represent the Variable regions of the Heavy chain of Heavy-chain only (VHH). Camelids make conventional immunoglobulin G (IgG), but the heavy chain only antibodies are encoded by distinct germ-line genes from IgG and represent approximately 30% of circulating antibodies Both sets of antibodies respond to immunogens by somatic rearrangement and mutation resulting in affinity maturation to synthesize high affinity specific antibodies. Alternative small protein fragments to VHH with specific ligand properties have been investigated for neutralization of HIV-1 and for exploitation as potential microbicides or therapeutics. They include, for example, the outer domains of the CD4 (cluster of differentiation antigen 4) receptor linked to an IgG framework [18] or expressed in an adeno-associated virus (AAV) vector [19], and designed ankyrin repeat proteins (‘Darpins’) [20,21]. In this review we focus on the properties and potential applications of HIV-1-neutralizing nanobodies
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