HIV envelope

Class

Broadly neutralizing antibody

The HIV envelope glycoprotein, often called Env, is a trimeric spike (built from gp120 and gp41 subunits) displayed on the surface of the virus. It is the sole viral protein exposed to the immune system and is required for the virus to attach to and fuse with host immune cells. Because Env mutates rapidly and is heavily shielded by sugar molecules (glycans), most antibodies the body makes against it fail to stop infection broadly. A subset of antibodies, called broadly neutralizing antibodies, instead recognize regions of Env that are conserved across many viral strains because they are functionally essential for entry, such as the site where Env binds the CD4 receptor. By binding these conserved regions, such antibodies can block entry of diverse circulating HIV strains rather than just one. This mechanism is being explored both as a passive treatment or prevention strategy, delivered as antibody drugs, and as the target of vaccine design efforts aimed at teaching the immune system to generate such antibodies on its own. Because a single antibody can be circumvented by viral mutation, most strategies pair antibodies against different conserved sites or combine antibody administration with other tools.