While the induction of a neutralizing antibody response against HIV remains a daunting goal, data from both natural infection and vaccine-induced immune responses suggest that it may be possible to induce antibodies with enhanced Fc effector activity and improved antiviral control via vaccination. However, the specific features of naturally induced HIV-specific antibodies that allow for the potent recruitment of antiviral activity and the means by which these functions are regulated are poorly defined. Because antibody effector functions are critically dependent on antibody Fc domain glycosylation, we aimed to define the natural glycoforms associated with robust Fc-mediated antiviral activity. We demonstrate that spontaneous control of HIV and improved antiviral activity are associated with a dramatic shift in the global antibody-glycosylation profile toward agalactosylated glycoforms. HIV-specific antibodies exhibited an even greater frequency of agalactosylated, afucosylated, and asialylated glycans. These glycoforms were associated with enhanced Fc-mediated reduction of viral replication and enhanced Fc receptor binding and were consistent with transcriptional profiling of glycosyltransferases in peripheral B cells. These data suggest that B cell programs tune antibody glycosylation actively in an antigen-specific manner, potentially contributing to antiviral control during HIV infection.
Margaret E. Ackerman, Max Crispin, Xiaojie Yu, Kavitha Baruah, Austin W. Boesch, David J. Harvey, Anne-Sophie Dugast, Erin L. Heizen, Altan Ercan, Ickwon Choi, Hendrik Streeck, Peter A. Nigrovic, Chris Bailey-Kellogg, Chris Scanlan, Galit Alter
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Breaking the Glyco-Code of HIV Persistence and Immunopathogenesis
F Colomb, LB Giron, I Trbojevic-Akmacic, G Lauc, M Abdel-Mohsen |
Current HIV/AIDS Reports | 2019 |
Fc Mediated Activity of Antibodies: Structural and Functional Diversity
JV Ravetch, F Nimmerjahn |
2019 | |
An Inflammatory Story: Antibodies in Tuberculosis Comorbidities
MR McLean, LL Lu, SJ Kent, AW Chung |
Frontiers in immunology | 2019 |
Antibody-Dependent Cellular Phagocytosis in Antiviral Immune Responses
MZ Tay, K Wiehe, J Pollara |
Frontiers in immunology | 2019 |
Extra-Neutralizing FcR-Mediated Antibody Functions for a Universal Influenza Vaccine
CM Boudreau, G Alter |
Frontiers in immunology | 2019 |
Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N -Glycosylation Profiles
KB Chandler, N Mehta, DR Leon, TJ Suscovich, G Alter, CE Costello |
Molecular & cellular proteomics : MCP | 2019 |
The Antibodiome—Mapping the Humoral Immune Response to HIV
AL Butler, S Fischinger, G Alter |
Current HIV/AIDS Reports | 2019 |
TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes
MH Schleimann, ML Kobberø, LK Vibholm, K Kjær, LB Giron, K Busman-Sahay, CN Chan, M Nekorchuk, M Schmidt, B Wittig, TE Damsgaard, P Ahlburg, MB Hellfritzsch, K Zuwala, FH Rothemejer, R Olesen, P Schommers, F Klein, H Dweep, A Kossenkov, JR Nyengaard, JD Estes, M Abdel-Mohsen, L Østergaard, M Tolstrup, OS Søgaard, PW Denton |
EBioMedicine | 2019 |
Response to immune complex vaccine in chronic hepatitis B patients is associated with lower baseline level of serum IgG galactosylation:
J Han, GZ Gong, JH Lei, WJ Qin, RH Qin, XY Wang, JX Gu, SF Ren, YM Wen |
Medicine | 2019 |
Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis
A Naegeli, E Bratanis, C Karlsson, O Shannon, R Kalluru, A Linder, J Malmström, M Collin |
Journal of Experimental Medicine | 2019 |
Multiple viral proteins and immune response pathways act to generate robust long-term immunity in Sudan virus survivors
A Sobarzo, SW Stonier, O Radinsky, S Gelkop, AI Kuehne, A Edri, AS Herbert, S Fedida-Metula, JJ Lutwama, V Yavelsky, C Davis, A Porgador, JM Dye, L Lobel |
EBioMedicine | 2019 |
Fc gamma receptor polymorphisms modulated the vaccine effect on HIV-1 risk in the HVTN 505 HIV vaccine trial
SS Li, PB Gilbert, LN Carpp, CW Pyo, H Janes, Y Fong, X Shen, SD Neidich, D Goodman, A deCamp, KW Cohen, G Ferrari, SM Hammer, ME Sobieszczyk, MJ Mulligan, SP Buchbinder, MC Keefer, E DeJesus, RM Novak, I Frank, MJ McElrath, GD Tomaras, DE Geraghty, X Peng |
Journal of virology | 2019 |
Understudied Factors Influencing Fc-Mediated Immune Responses against Viral Infections
SP Anand, A Finzi |
Human vaccines | 2019 |
IgG Fc glycosylation as an axis of humoral immunity in childhood
HD Cheng, I Tirosh, N de Haan, H Stöckmann, B Adamczyk, CA McManus, R OFlaherty, G Greville, R Saldova, F Bonilla, LD Notarangelo, GJ Driessen, IA Holm, PM Rudd, M Wuhrer, ME Ackerman, PA Nigrovic |
Journal of Allergy and Clinical Immunology | 2019 |
Primary Human Natural Killer Cells Retain Proinflammatory IgG1 at the Cell Surface and Express CD16a Glycoforms with Donor-dependent Variability
KR Patel, JD Nott, AW Barb |
Molecular & cellular proteomics : MCP | 2019 |
A MUC16 IgG Binding Activity Selects for a Restricted Subset of IgG Enriched for Certain Simian Immunodeficiency Virus Epitope Specificities
JR Schneider, X Shen, C Orlandi, T Nyanhete, S Sawant, AM Carias, AD Smith, NL Kelleher, RS Veazey, GK Lewis, GD Tomaras, TJ Hope, G Silvestri |
Journal of virology | 2019 |
Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization
B Su, S Dispinseri, V Iannone, T Zhang, H Wu, R Carapito, S Bahram, G Scarlatti, C Moog |
Frontiers in immunology | 2019 |
Longitudinal Antibody Responses in People Who Inject Drugs Infected With Similar Human Immunodeficiency Virus Strains
AD Redd, NA Doria-Rose, JA Weiner, M Nason, M Seivers, SD Schmidt, O Laeyendecker, C Martens, D Bruno, BF Keele, N Raju, IS Georgiev, SL Lamers, J Astemborski, GD Kirk, JR Mascola, ME Ackerman, SH Mehta, TC Quinn |
The Journal of Infectious Diseases | 2019 |
Engineering the interactions between a plant‐produced HIV antibody and human Fc receptors
S Stelter, MJ Paul, AY Teh, M Grandits, F Altmann, J Vanier, M Bardor, A Castilho, RL Allen, JK Ma |
Plant Biotechnology Journal | 2019 |
Monitoring of immunoglobulin N- and O-glycosylation in health and disease
N de Haan, D Falck, M Wuhrer |
Glycobiology | 2019 |