Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants

• Published in: Virology (New York, N.Y.) N.Y.), 2013-11, Vol.446 (1), p.56-65
• Main Authors: Feng, Yu, Forsell, Mattias N.E, Flynn, Barbara, Adams, William, Loré, Karin, Seder, Robert, Wyatt, Richard T, Karlsson Hedestam, Gunilla B
• Format: Article
• Language: English
• Subjects: CD4 Antigens - metabolism; Cross-linker; Epitopes - immunology; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV-1 - immunology; HIV-1 envelope glycoprotein; Human immunodeficiency virus 1; Humans; Infectious Disease; Neutralizing antibody; Protein Binding; Toll-Like Receptor 7 - chemistry; Toll-Like Receptor 7 - immunology; Toll-Like Receptor 7 - metabolism; Toll-like receptor ligand
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2013.07.028

Abstract 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.