Document text
Principal Investigator: Isaac Jonathan Krauss
Organization: BRANDEIS UNIVERSITY
Fiscal Year: 2024
Award: $203,125
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract
HIV broadly neutralizing antibodies (bnAbs) most commonly target the High Mannose Patch (HMP), a
mannose-rich region of HIV Env in the vicinity of the V3 loop and the N332 glycan. HMP bnAbs (e.g.,
2G12, PGT128, BG18) tend to recognize non-reducing-terminal Man1α-2Man moieties within
oligomannose glycans; however, in immunizations with oligomannose glycoconjugates, antibodies are
rarely raised against Man1a-2Man, and instead bind to core motifs of the glycan. We hypothesize that in
vivo mannosidase trimming of Man1a-2Man termini is a major reason why antibodies do not develop
against this motif. In Aim 1, we will prepare stabilized oligomannose glycans, in which a sulfur linkage
prevents mannosidase cleavage of the Man1α-2Man, but structurally mimics the natural glycan and is
recognized by bnAbs. In Aim 2, we will immunize rabbits with CRM197 glycoconjugates containing the
stabilized or unstabilized glycans and compare the resulting antibodies’ HIV Env binding and
neutralization activity. We will also intensively characterize the ability of these antibodies to bind Man1a-
2Man using an oligomannose-focused glycan array.
Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Affinity><Antibodies><Antibody Response><Antigenic Determinants><Antigens><Binding><Binding Determinants><Blood Serum><CRM-197><CRM197><Carbohydrates><Carrier Proteins><Collaborations><D-Mannose><Disaccharides><Domestic Rabbit><ELISA><Enzyme-Linked Immunosorbent Assay><Epitopes><Family><Family member><Germinal Center><Glycans><Glycoconjugates><Glycopeptides><Goals><HIV><HIV Antibodies><HIV Envelope Glycoprotein gp120><HIV Envelope Protein gp120><HIV Infections><HIV env Protein gp120><HIV-Associated Antibodies><HTLV-III Antibodies><HTLV-III Infections><HTLV-III gp120><HTLV-III-LAV Antibodies><HTLV-III-LAV Infections><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Antibodies><Human T-Lymphotropic Virus Type III Infections><Hydrophobicity><Immunization><Immunize><Infection><LAV Antibodies><LAV-HTLV-III><Laboratories><Length><Lymphadenopathy-Associated Antibodies><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca mulatta><Man9GlcNAc2><Mannopyranose><Mannopyranoside><Mannose><Mannosidase><Memory B Cell><Memory B-Lymphocyte><Metabolic Glycosylation><Methods><Modification><Molecular Interaction><O element><O2 element><Oryctolagus cuniculus><Oxygen><Patients><Peptides><Polysaccharides><Proteins><Rabbits><Rabbits Mammals><Rhesus Macaque><Rhesus Monkey><S element><Serum><Single Crystal Diffraction><Structure><Structure of germinal center of lymph node><Sulfur><Surface><Testing><Transport Protein Gene><Transport Proteins><Transporter Protein><V3 Loop><V3 Loop of HIV-1><Vaccination><Vaccines><Variant><Variation><Virus><Virus-HIV><X Ray Crystallographies><X-Ray Crystallography><X-Ray Diffraction Crystallography><X-Ray/Neutron Crystallography><Xray Crystallography><analog><arm><cross reacting material 197><enzyme linked immunoassay><glycosylation><gp120><gp120 ENV Glycoprotein><gp120(HIV)><immunogen><immunogenicity><improved><in vivo><man><mannosyl(9)-N-acetylglucosamine2><neutralizing antibody><prevent><preventing><response>