Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants.
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.
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA; IAVI Center for Neutralizing Antibodies, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yu
Y
Feng
Mattias N E
MN
Forsell
Barbara
B
Flynn
William
W
Adams
Karin
K
Loré
Robert
R
Seder
Richard T
RT
Wyatt
Gunilla B
GB
Karlsson Hedestam
D015704:CD4 Antigens / Q000378:metabolism; D000939:Epitopes / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011485:Protein Binding; D051199:Toll-Like Receptor 7 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D051199:Toll-Like Receptor 7; C514793:gp120 protein, Human immunodeficiency virus 1
Cross-linker; HIV-1 envelope glycoprotein; Neutralizing antibody; Toll-like receptor ligand