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

TitleChemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants.
Publication TypeJournal Article
Year of Publication2013
AuthorsFeng Y, Forsell MNE, Flynn B, Adams W, Loré K, Seder R, Wyatt RT, Karlsson Hedestam GB
JournalVirology
Volume446
Issue1-2
Pagination56-65
Date Published11/01/2013
ISSN1096-0341
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.

DOI10.1016/j.virol.2013.07.028
Alternate JournalVirology
PubMed ID24074567
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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