Saheli Sadanand1,2, Jishnu Das1,3,2, Amy W Chung1,4,2, Matthew K Schoen1, Sophie Lane1, Todd J Suscovich1, Hendrik Streeck5, Davey M Smith6, Susan J Little6, Douglas A Lauffenburger3, Douglas D Richman7,8, Galit Alter1. 1. Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, USA. 2. Saheli Sadanand, Jishnu Das and Amy W. Chung contributed equally to the article. 3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. 4. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia. 5. Institut für HIV Forschung, Universität Duisburg-Essen, Essen, Germany. 6. Department of Medicine, Division of Infectious Diseases, University of California San Diego, San Diego, California. 7. VA San Diego Healthcare System. 8. Department of Pathology, School of Medicine, University of California San Diego, San Diego, California, USA.
Abstract
OBJECTIVE: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between patients who ultimately became controllers versus those who became progressors. METHODS: IgG was purified from plasma from nine acutely infected patients who subsequently controlled HIV spontaneously (controllers) and 10 acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 postinfection. Levels of clade B gp120-specific, gp140-specific and gp41-specific IgG antibody subclasses were measured. In addition, gp120-specific antibody-dependent cellular phagocytosis, rapid fluorescent antibody-dependent cellular cytotoxicity and antibody-dependent cellular viral inhibition were all assessed. RESULTS: Although no single antibody-related measurement was significantly associated with long-term HIV control, combinations of antibody-associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 antibodies and losses in Env-specific IgG3 antibodies. Moreover, progressors, but not controllers, lost antibody-dependent cellular viral inhibition function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection. CONCLUSION: This study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir.
OBJECTIVE: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between patients who ultimately became controllers versus those who became progressors. METHODS: IgG was purified from plasma from nine acutely infectedpatients who subsequently controlled HIV spontaneously (controllers) and 10 acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 postinfection. Levels of clade B gp120-specific, gp140-specific and gp41-specific IgG antibody subclasses were measured. In addition, gp120-specific antibody-dependent cellular phagocytosis, rapid fluorescent antibody-dependent cellular cytotoxicity and antibody-dependent cellular viral inhibition were all assessed. RESULTS: Although no single antibody-related measurement was significantly associated with long-term HIV control, combinations of antibody-associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 antibodies and losses in Env-specific IgG3 antibodies. Moreover, progressors, but not controllers, lost antibody-dependent cellular viral inhibition function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection. CONCLUSION: This study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir.
Authors: Susanne E Johansson; Erik Rollman; Amy W Chung; Rob J Center; Bo Hejdeman; Ivan Stratov; Jorma Hinkula; Britta Wahren; Klas Kärre; Stephen J Kent; Louise Berg Journal: Viral Immunol Date: 2011-09-29 Impact factor: 2.257
Authors: Davey M Smith; Matthew C Strain; Simon D W Frost; Satish K Pillai; Joseph K Wong; Terri Wrin; Yang Liu; Christos J Petropolous; Eric S Daar; Susan J Little; Douglas D Richman Journal: Virology Date: 2006-09-07 Impact factor: 3.616
Authors: Donald N Forthal; Gary Landucci; Haitao Ding; John C Kappes; Angela Wang; Irene Thung; Tran Phan Journal: AIDS Date: 2011-11-13 Impact factor: 4.177
Authors: Eric P Brown; Anna F Licht; Anne-Sophie Dugast; Ickwon Choi; Chris Bailey-Kellogg; Galit Alter; Margaret E Ackerman Journal: J Immunol Methods Date: 2012-09-27 Impact factor: 2.303
Authors: Anne-Sophie Dugast; Leonidas Stamatatos; Andrew Tonelli; Todd J Suscovich; Anna F Licht; Iliyana Mikell; Margaret E Ackerman; Hendrik Streeck; P J Klasse; John P Moore; Galit Alter Journal: Eur J Immunol Date: 2014-08-11 Impact factor: 5.532
Authors: Amy W Chung; Manu P Kumar; Kelly B Arnold; Wen Han Yu; Matthew K Schoen; Laura J Dunphy; Todd J Suscovich; Nicole Frahm; Caitlyn Linde; Alison E Mahan; Michelle Hoffner; Hendrik Streeck; Margaret E Ackerman; M Juliana McElrath; Hanneke Schuitemaker; Maria G Pau; Lindsey R Baden; Jerome H Kim; Nelson L Michael; Dan H Barouch; Douglas A Lauffenburger; Galit Alter Journal: Cell Date: 2015-11-05 Impact factor: 41.582
Authors: Margaret McManus; Jennifer Henderson; Anita Gautam; Robin Brody; Eric R Weiss; Deborah Persaud; Eric Mick; Katherine Luzuriaga Journal: Clin Infect Dis Date: 2019-05-02 Impact factor: 9.079
Authors: Evan D Rossignol; Anne-Sophie Dugast; Hacheming Compere; Christopher A Cottrell; Jeffrey Copps; Shu Lin; Deniz Cizmeci; Michael S Seaman; Margaret E Ackerman; Andrew B Ward; Galit Alter; Boris Julg Journal: Cell Rep Date: 2021-05-25 Impact factor: 9.423
Authors: Stian Foss; Maria Bottermann; Alexandra Jonsson; Inger Sandlie; Leo C James; Jan Terje Andersen Journal: Front Immunol Date: 2019-08-28 Impact factor: 7.561