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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Malignant tissues produce divergent antibody glycosylation of relevance for cancer gene therapy effectiveness
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Journal of Experimental Medicine | 2020 |
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IBMS BoneKEy | 2020 |
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C Atyeo, KM Pullen, EA Bordt, S Fischinger, J Burke, A Michell, MD Slein, C Loos, LL Shook, AA Boatin, LJ Yockey, D Pepin, MC Meinsohn, NM Nguyen, M Chauvin, D Roberts, IT Goldfarb, JD Matute, KE James, LM Yonker, LM Bebell, AJ Kaimal, KJ Gray, D Lauffenburger, AG Edlow, G Alter |
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Profiling of Naturally Occurring Antibodies to the Thomsen-Friedenreich Antigen in Health and Cancer: The Diversity and Clinical Potential
O Kurtenkov |
BioMed Research International | 2020 |
Mining for humoral correlates of HIV control and latent reservoir size
J Das, A Devadhasan, C Linde, T Broge, J Sassic, M Mangano, S O'Keefe, T Suscovich, H Streeck, A Irrinki, C Pohlmeyer, G Min-Oo, S Lin, JA Weiner, T Cihlar, ME Ackerman, B Julg, S Deeks, DA Lauffenburger, G Alter, DC Douek |
PLoS pathogens | 2020 |
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LL Lu, J Das, PS Grace, SM Fortune, BI Restrepo, G Alter |
The Journal of Infectious Diseases | 2020 |
Distinct Immunoglobulin Fc Glycosylation Patterns Are Associated with Disease Nonprogression and Broadly Neutralizing Antibody Responses in Children with HIV Infection
M Muenchhoff, AW Chung, J Roider, AS Dugast, S Richardson, H Kløverpris, A Leslie, T Ndungu, P Moore, G Alter, PJ Goulder, HF Rosenberg |
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Sensitivity analysis based on the random forest machine learning algorithm identifies candidate genes for regulation of innate and adaptive immune response of chicken
A Polewko-Klim, W Lesiński, AK Golińska, K Mnich, M Siwek, WR Rudnicki |
Poultry science | 2020 |
Tracking the Trajectory of Functional Humoral Immune Responses Following Acute HIV Infection
MF Jennewein, J Mabuka, CL Papia, CM Boudreau, KL Dong, ME Ackerman, T Ndung'u, G Alter |
Frontiers in immunology | 2020 |
Interferon-α alters host glycosylation machinery during treated HIV infection
LB Giron, F Colomb, E Papasavvas, L Azzoni, X Yin, M Fair, A Anzurez, M Damra, K Mounzer, JR Kostman, P Tebas, U O'Doherty, H Tateno, Q Liu, MR Betts, LJ Montaner, M Abdel-Mohsen |
EBioMedicine | 2020 |
Antibody-Dependent Cellular Phagocytosis of HIV-1-Infected Cells Is Efficiently Triggered by IgA Targeting HIV-1 Envelope Subunit gp41
M Duchemin, D Tudor, A Cottignies-Calamarte, M Bomsel |
Frontiers in immunology | 2020 |
Polyfunctional Fc Dependent Activity of Antibodies to Native Trimeric Envelope in HIV Elite Controllers
S Kant, N Zhang, A Barbé, JP Routy, C Tremblay, R Thomas, J Szabo, P Côté, B Trottier, R LeBlanc, D Rouleau, M Harris, FP Dupuy, NF Bernard |
Frontiers in immunology | 2020 |
Understanding the role of antibody glycosylation through the lens of severe viral and bacterial diseases
EB Irvine, G Alter |
Glycobiology | 2020 |
Plasma and antibody glycomic biomarkers of time to HIV rebound and viral setpoint
LB Giron, E Papasavvas, L Azzoni, X Yin, A Anzurez, M Damra, K Mounzer, JR Kostman, I Sanne, CS Firnhaber, H Tateno, Q Liu, LJ Montaner, M Abdel-Mohsen |
AIDS | 2020 |