|Title||Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Feng Y, Forsell MNE, Flynn B, Adams W, Loré K, Seder R, Wyatt RT, Karlsson Hedestam GB|
Covalent conjugation of immune-stimulatory compounds to protein antigens is a potential means to self-adjuvant non-replicating subunit vaccines. Previously, it was demonstrated that covalent coupling of a Toll-like receptor (TLR) ligand to the exterior HIV-1 envelope glycoprotein, gp120, enhanced its immunogenicity. However, the consequences of chemical conjugation to gp120 on broadly neutralizing antibody (bNAb) epitopes were so far not examined. Here, we conjugated a TLR7/8 ligand to lysine residues on gp120 using NHS-PEO8-maleimide linkers and investigated if this affected Ab recognition of the CD4 binding site (CD4bs), a highly conserved target for bNAbs. We demonstrate that the recognition of the CD4bs was reduced following coupling, especially at a higher coupling ratio. These results have implications for the coupling of ligands to vaccine antigens where elicitation of humoral immune responses to specific neutralizing determinants is desired.
|Grant List||UM1 AI100663 / AI / NIAID NIH HHS / United States|
Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants.