Aggregate complexes of HIV-1 induced by multimeric antibodies.
Abstract
BACKGROUND: Antibody mediated viral aggregation may impede viral transfer across mucosal
surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing
inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal
CD4 T cells and dendritic cells. These functions may work together to provide effective
immune exclusion of virus from mucosal tissue; however little is known about the antibody
characteristics required to induce HIV aggregation. Such knowledge may be critical
to the design of successful immunization strategies to facilitate viral immune exclusion
at the mucosal portals of entry. RESULTS: The potential of neutralizing and non-neutralizing
IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic
light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal
HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming
viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable
viral aggregate populations that could be separated from uncomplexed virions. Epitope
specificity influenced both the degree of aggregation and formation of higher order
complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders
were able to efficiently opsonize viral particles in the absence of significant aggregation,
reflective of monomeric IgA. CONCLUSIONS: These results collectively demonstrate that
dIgA is capable of forming stable viral aggregates providing a plausible basis for
testing the effectiveness of aggregation as a potential protection mechanism at the
mucosal portals of viral entry.
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https://hdl.handle.net/10161/14673Published Version (Please cite this version)
10.1186/s12977-014-0078-8Publication Info
Stieh, Daniel J; King, Deborah F; Klein, Katja; Liu, Pinghuang; Shen, Xiaoying; Hwang,
Kwan Ki; ... Shattock, Robin J (2014). Aggregate complexes of HIV-1 induced by multimeric antibodies. Retrovirology, 11. pp. 78. 10.1186/s12977-014-0078-8. Retrieved from https://hdl.handle.net/10161/14673.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Guido Ferrari
Professor in Surgery
The activities of the Ferrari Laboratory are based on both independent basic research
and immune monitoring studies. The research revolves around three main areas of interest:
class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity
(ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With
continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation
along with many other productive collaborations wi
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine
Research & Development in the Department of Surgery, Division of Surgical Sciences
at Duke University Medical Center. His major research interests are viral immunology
and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing
antibodies. Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory,
including mechanisms of neutralization and escape,
Xiaoying Shen
Associate Professor in Surgery
Dr. Shen is an Associate Director and Deputy of the Laboratory for HIV and COVID-19
Vaccine Research & Development in the Department of Surgery, Division of Surgical
Sciences at Duke University Medical Center. Her research interest focuses on the humoral
immune response following virus infection or vaccination. During the past decade,
she has worked intensively on the specificity and breadth of binding antibody responses
against HIV. Dr. Shen’s team developed assays and
Georgia Doris Tomaras
Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor
of Molecular Genetics and Microbiology and is a Fellow of the American Academy of
Microbiology (AAM) and a Fellow of the American Association for the Advancement of
Science (AAAS). Dr. Tomaras is Co-Director of the Center for Human Systems Immunology
(CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her
national and international leadership roles i
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