2G12 antibody (2G12)

2G12 is a human monoclonal antibody of the IgG1 subclass that was isolated from an HIV-1 infected individual and is capable of broad and potent neutralization of various HIV-1 strains[1][7]. It is unique among antibodies in that it recognizes a cluster of N-linked high-mannose glycans on the outer domain of the gp120 envelope glycoprotein, binding through a rare domain-exchanged structure that increases its affinity for these glycan epitopes[5][7][9]. The key target residues for 2G12 binding are the glycans at Asn 295 and 332, with contributions from adjacent glycosylation sites[7][8]. By binding these glycans, 2G12 blocks HIV-1's ability to interact with cellular receptors (CD4 and coreceptors), thereby preventing virus entry and cell infection[8]. 2G12's high specificity for oligomannose-type glycans means its effectiveness is determined by the presence of these carbohydrate structures on different HIV-1 isolates. It is considered a model for glycan-targeting broadly neutralizing antibodies and serves as a prototype for HIV vaccine design that aims to elicit similar responses[2][5]. Recent research indicates that 2G12 can bind high-mannose glycans on glycoproteins from other viruses (e.g., influenza, SARS-CoV-2), but its main relevance remains in HIV/AIDS therapy and prevention[5]. 2G12 is not itself a therapeutic "target" (such as a receptor or enzyme), but is a therapeutic agent used to target viral antigens.

Other names

2G12Human anti-HIV-1 gp120 monoclonal antibodyBroadly neutralizing antibody 2G12

Binds to high-mannose glycans on HIV-1 gp120 envelope glycoprotein, preventing the virus from attaching to and entering host cells[1][7]. Blocks viral coreceptor interactions (CD4 and CCR5)[8].