Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection
Pinghuang Liu,R. Glenn Overman,Nicole L. Yates,S. Munir Alam,Nathan Vandergrift,Yue Chen,Frederik Graw,Stephanie A. Freel,John C. Kappes,Christina Ochsenbauer,David C. Montefiori,Feng Gao,Alan S. Perelson,Myron S. Cohen,Barton F. Haynes,Georgia D. Tomaras +15 more
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TLDR
The composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection.Abstract:
Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent transmission by neutralization of virus or mechanically prevent HIV-1 migration through mucosal layers. In this study, we quantified circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of AHI subjects, and compared the levels and antibody specificity to those in chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes) were in significantly lower levels relative to the viral load in acute infection than in chronic HIV-1 infection. The specificities of the antibodies in the immune complexes differed between acute and chronic infection (anti-gp41 Ab in acute infection and anti-gp120 in chronic infection), potentially suggesting different roles in immunopathogenesis for complexes arising at different stages of infection. We also determined the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that the composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection.read more
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Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination
Nicole L. Yates,Nicole L. Yates,Hua-Xin Liao,Hua-Xin Liao,Youyi Fong,Allan C. deCamp,Nathan Vandergrift,Nathan Vandergrift,William T. Williams,William T. Williams,S. Munir Alam,S. Munir Alam,Guido Ferrari,Guido Ferrari,Zhi Yong Yang,Kelly E. Seaton,Kelly E. Seaton,Phillip W. Berman,Michael D. Alpert,David T. Evans,Robert J. O'Connell,Donald P. Francis,Faruk Sinangil,Carter Lee,Sorachai Nitayaphan,Supachai Rerks-Ngarm,Jaranit Kaewkungwal,Punnee Pitisuttithum,James Tartaglia,Abraham Pinter,Susan Zolla-Pazner,Peter B. Gilbert,Gary J. Nabel,Nelson L. Michael,Jerome H. Kim,David C. Montefiori,David C. Montefiori,Barton F. Haynes,Barton F. Haynes,Georgia D. Tomaras +39 more
TL;DR: HIV-1–specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine, and should be evaluated in future HIV-1 vaccine efficacy trials to further refine immune correlates of protection.
Journal ArticleDOI
Vaccine Induction of Antibodies against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2
Hua-Xin Liao,Mattia Bonsignori,S. Munir Alam,Jason S. McLellan,Georgia D. Tomaras,M. Anthony Moody,Daniel M. Kozink,Kwan Ki Hwang,Xi Chen,Chun Yen Tsao,Pinghuang Liu,Xiaozhi Lu,Robert Parks,David C. Montefiori,Guido Ferrari,Justin Pollara,Mangala Rao,Kristina K. Peachman,Sampa Santra,Norman L. Letvin,Nicos Karasavvas,Zhi-Yong Yang,Kaifan Dai,Marie Pancera,Jason Gorman,Kevin Wiehe,Nathan I. Nicely,Supachai Rerks-Ngarm,Sorachai Nitayaphan,Jaranit Kaewkungwal,Punnee Pitisuttithum,James Tartaglia,Faruk Sinangil,Jerome H. Kim,Nelson L. Michael,Thomas B. Kepler,Peter D. Kwong,John R. Mascola,Gary J. Nabel,Abraham Pinter,Susan Zolla-Pazner,Susan Zolla-Pazner,Barton F. Haynes +42 more
TL;DR: Four V2 monoclonal antibodies from RV144 vaccinees are isolated that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV- 1-infected CD4(+) T cells, providing vaccine designers with new options.
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Generation of Transmitted/Founder HIV-1 Infectious Molecular Clones and Characterization of their Replication Capacity in CD4 T-Lymphocytes and Monocyte-derived Macrophages
Christina Ochsenbauer,Tara G. Edmonds,Haitao Ding,Brandon F. Keele,Julie M. Decker,Maria G. Salazar,Jesus F. Salazar-Gonzalez,Robin J. Shattock,Barton F. Haynes,George M. Shaw,Beatrice H. Hahn,John C. Kappes +11 more
TL;DR: It is suggested that the acquisition of clinical HIV-1 subtype B infection occurs by mucosal exposure to virus that is not highly macrophage tropic and that the generation and initial biological characterization of 10 clade B T/F infectious molecular clones provides new opportunities to probe virus-host interactions involved in HIV- 1 transmission.
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HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities.
Justin Pollara,Mattia Bonsignori,M. Anthony Moody,Pinghuang Liu,S. Munir Alam,Kwan-Ki Hwang,Thaddeus C. Gurley,Daniel M. Kozink,Lawrence C. Armand,Dawn J. Marshall,John F. Whitesides,Jaranit Kaewkungwal,Sorachai Nitayaphan,Punnee Pitisuttithum,Supachai Rerks-Ngarm,Merlin L. Robb,Robert J. O'Connell,Jerome H. Kim,Nelson L. Michael,David C. Montefiori,Georgia D. Tomaras,Hua-Xin Liao,Barton F. Haynes,Guido Ferrari +23 more
TL;DR: It is demonstrated that vaccine-induced HIV-1 envelope variable region 2 and constant region 1 antibodies synergize for recognition of virus-infected cells, infectious virion capture, virus neutralization, and antibody-dependent cellular cytotoxicity.
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Antibody-Dependent Cellular Phagocytosis in Antiviral Immune Responses.
TL;DR: It is proposed that additional investigation into the role of ADCP in protective viral responses, the specific virus epitopes targeted by ADCP antibodies, and the types of phagocytes and Fc receptors involved in ADCP at sites of virus infection will provide insight into strategies to successfully leverage this important immune response for improved antiviral immunity through rational vaccine design.
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