Composite C5–gp41 Kennedy Epitope interface epitope (C5–gp41 KE)

The Composite C5–gp41 Kennedy Epitope (KE) interface epitope is a quaternary structural site on the HIV-1 envelope glycoprotein (Env) complex. It is formed by the spatial proximity and interaction of the fifth constant (C5) region of the gp120 subunit (residues 501–512) and the Kennedy Epitope (KE) located within the gp41 subunit (residues 732–744). This interface plays a vital role in the non-covalent association between gp120 and gp41, helping to maintain the Env trimer in its metastable pre-fusion state. Although the Kennedy Epitope is traditionally considered part of the gp41 cytoplasmic tail, research suggests it may become exposed on the virion surface during fusion or through membrane-spanning loops, allowing it to interact with the gp120 C5 region. Antibodies that recognize this composite epitope are generally non-neutralizing but are clinically significant as their presence correlates with slower disease progression and reduced viral loads in HIV-1 infected patients. The therapeutic vaccine candidate Vacc-C5 is specifically designed to induce antibodies against this interface to stabilize the Env complex, prevent gp120 shedding, and mitigate the chronic immune activation that drives HIV pathogenesis.

Other names

C5/gp41 732-744 epitopeVacc-C5 epitopegp120 C5-gp41 KE interfaceC5-gp41 Kennedy epitopeC5-gp41 association site

Induction of non-neutralizing antibodies that stabilize the HIV-1 envelope glycoprotein complex and reduce chronic immune activation.