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Aggregate complexes of HIV-1 induced by multimeric antibodies.

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Date
2014-10-02
Authors
Stieh, Daniel J
King, Deborah F
Klein, Katja
Liu, Pinghuang
Shen, Xiaoying
Hwang, Kwan Ki
Ferrari, Guido
Montefiori, David C
Haynes, Barton
Pitisuttithum, Punnee
Kaewkungwal, Jaranit
Nitayaphan, Sorachai
Rerks-Ngarm, Supachai
Michael, Nelson L
Robb, Merlin L
Kim, Jerome H
Denny, Thomas N
Tomaras, Georgia D
Shattock, Robin J
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(19 total)
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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.
Type
Journal article
Subject
Antibodies, Monoclonal
HIV Antibodies
HIV-1
Humans
Immunoglobulin A
Immunoglobulin G
Permalink
https://hdl.handle.net/10161/14673
Published Version (Please cite this version)
10.1186/s12977-014-0078-8
Publication 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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Scholars@Duke

Denny

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
Ferrari

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
Haynes

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
Montefiori

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,
Shen

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
Tomaras

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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