Antibodies against Manalpha1,2-Manalpha1,2-Man oligosaccharide structures recognize envelope glycoproteins from HIV-1 and SIV strains.

Glycobiology
Robert J LuallenYu Geng

Abstract

Design of an envelope glycoprotein (Env)-based vaccine against human immunodeficiency virus type-1 (HIV-1) is complicated by the large number of N-linked glycans that coat the protein and serve as a barrier to antibody-mediated neutralization. Compared to normal mammalian glycoproteins, high-mannose-type glycans are disproportionately represented on the gp120 subunit of Env. These N-glycans serve as a target for a number of anti-HIV molecules that bind terminal alpha1,2-linked mannose residues, including lectins and the monoclonal antibody 2G12. We created a Saccharomyces cerevisiae glycosylation mutant, Deltamnn1Deltamnn4, to expose numerous terminal Manalpha1,2-Man residues on endogenous hypermannosylated glycoproteins in the yeast cell wall. Immunization of rabbits with whole cells from this mutant induced antibodies that bound to a broad range of Env proteins, including clade A, B, and C of HIV and simian immunodeficiency virus (SIV). The gp120 binding activity of these immune sera was due to mannose-specific immunoglobulin, as removal of high-mannose glycans and alpha1,2-linked mannoses from gp120 abrogated serum binding. Glycan array analysis with purified IgG demonstrated binding mainly to glycans with Manalpha1,2-Manalp...Continue Reading

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Citations

Aug 29, 2013·Nature Structural & Molecular Biology·Max Crispin, Thomas A Bowden
Jul 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Katie J DooresChristopher N Scanlan
Dec 12, 2012·Journal of Virology·Katie J DooresDennis R Burton
Dec 14, 2011·Journal of Virology·Christy L LavineUNKNOWN NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
Jan 14, 2011·Bioscience, Biotechnology, and Biochemistry·Mariko KimuraYoshinobu Kimura
Feb 22, 2012·Biosensors & Bioelectronics·Oscar NorbergOlof Ramström
Jun 26, 2010·Medicinal Research Reviews·K O François, J Balzarini
Feb 10, 2011·Chemical Communications : Chem Comm·Giovanni Di FabioLorenzo De Napoli
Aug 21, 2013·Psychotherapy Research : Journal of the Society for Psychotherapy Research·Anna Karin SöderbergRolf Holmqvist
May 4, 2016·Psychotherapy Research : Journal of the Society for Psychotherapy Research·Mattias Holmqvist LarssonRolf Holmqvist
Dec 19, 2019·Viral Immunology·J Stewart NewJohn F Kearney
Aug 1, 2013·Chemical Science·Roberto AdamoGonçalo J L Bernardes

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