HIV-1 envelope glycoprotein gp120 CD4-binding site (CD4bs) (HIV-1 gp120 CD4bs)

The HIV-1 envelope glycoprotein gp120 CD4-binding site (CD4bs) is a highly conserved region of the HIV-1 virus that facilitates entry into host cells by binding to the CD4 receptor (Jardine et al., 2013, Science). As a critical site for viral infectivity, it is a major target for the induction of broadly neutralizing antibodies (bnAbs) which can neutralize a wide range of HIV-1 variants. The eOD-GT8 (Engineered Outer Domain Germline-Targeting 8) is a computationally designed protein immunogen that mimics the CD4bs epitope. It was specifically engineered to bind with high affinity to the germline precursors of VRC01-class antibodies, which are otherwise difficult to activate with natural HIV-1 envelope proteins (Jardine et al., 2016, Science). By targeting these specific B cell lineages, eOD-GT8 serves as a priming immunogen in a multi-stage vaccine strategy intended to guide the immune system toward producing mature, protective bnAbs. This approach addresses the significant challenge of HIV-1's extreme genetic diversity and its ability to evade the immune system through glycan shielding and conformational masking (Leggat et al., 2022, Science).

Other names

CD4-binding siteCD4bseOD-GT8Engineered Outer Domain Germline-Targeting 8eOD-GT8 60merHIV-1 gp120 CD4bs epitope

Germline-targeting vaccine strategy designed to activate specific B cell precursors capable of evolving into broadly neutralizing antibodies (bnAbs) against the HIV-1 CD4-binding site (Leggat et al., 2022, Science).