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Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission.

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Date
2015-07-01
Authors
Permar, Sallie R
Fong, Youyi
Vandergrift, Nathan
Fouda, Genevieve G
Gilbert, Peter
Parks, Robert
Jaeger, Frederick H
Pollara, Justin
Martelli, Amanda
Liebl, Brooke E
Lloyd, Krissey
Yates, Nicole L
Overman, R Glenn
Shen, Xiaoying
Whitaker, Kaylan
Chen, Haiyan
Pritchett, Jamie
Solomon, Erika
Friberg, Emma
Marshall, Dawn J
Whitesides, John F
Gurley, Thaddeus C
Von Holle, Tarra
Martinez, David R
Cai, Fangping
Kumar, Amit
Xia, Shi-Mao
Lu, Xiaozhi
Louzao, Raul
Wilkes, Samantha
Datta, Saheli
Sarzotti-Kelsoe, Marcella
Liao, Hua-Xin
Ferrari, Guido
Alam, S Munir
Montefiori, David C
Denny, Thomas N
Moody, M Anthony
Tomaras, Georgia D
Gao, Feng
Haynes, Barton F
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(41 total)
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Abstract
Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1-transmitting mothers and 165 propensity score-matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1-infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3-specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT.
Type
Journal article
Subject
AIDS Vaccines
Antibodies, Neutralizing
Antibody Specificity
Antigens, Viral
Cohort Studies
Female
HIV Antibodies
HIV Envelope Protein gp120
HIV Infections
HIV-1
Humans
Immunoglobulin G
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical
Logistic Models
Multivariate Analysis
Peptide Fragments
Pregnancy
Pregnancy Complications, Infectious
Risk Factors
Permalink
https://hdl.handle.net/10161/12060
Published Version (Please cite this version)
10.1172/JCI81593
Publication Info
Permar, Sallie R; Fong, Youyi; Vandergrift, Nathan; Fouda, Genevieve G; Gilbert, Peter; Parks, Robert; ... Haynes, Barton F (2015). Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission. J Clin Invest, 125(7). pp. 2702-2706. 10.1172/JCI81593. Retrieved from https://hdl.handle.net/10161/12060.
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

Alam

S. Munir Alam

Professor in Medicine
Research Interests.  The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
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) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), 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. He has recently been appointed to the Duke University Fuqua School of Business Health Sector Advisory Council. Previously, he was an Associate Professor of Pathology, Laboratory M
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
Fouda

Genevieve Giny Fouda

Associate Professor in Pediatrics
Dr Fouda's research interest is in understanding infant immune responses in the setting of infection and vaccination. Her current work focuses on HIV mother to child transmission.
Gao

Feng Gao

Professor Emeritus in Medicine
Dr. Feng Gao is Professor of Medicine at Duke University. The Gao laboratory has a long-standing interest in elucidating the origins and evolution of human and simian inmmunodeficiency viruses (HIV and SIV), and in studying HIV/SIV gene function and pathogenic mechanisms from the evolutionary perspective. These studies have led to new strategies to better understand HIV origins,  biology, pathogenesis and drug resistance, and to design new AIDS vaccines.
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
Liao

Hua-Xin Liao

Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
Montefiori

David Charles Montefiori

Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for AIDS Vaccine Research and Development in the Department of Surgery, Division of Surgical Sciences, Duke University Medical Center. His major research interests are viral immunology and AIDS vaccine development, with a special emphasis on neutralizing antibodies. One of his highest priorities is to identify immunogens that generate broadly cross-reactive neutralizing antibodies for inclusion in HIV vaccines.  Many aspects of the
Moody

Michael Anthony Moody

Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious Diseases and Professor in the Department of Immunology at Duke University Medical Center. Research in the Moody lab is focused on understanding the B cell responses during infection, vaccination, and disease. The lab has become a resource for human phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine Institute (DHVI). The Moody lab is currently funded to study influenza, syphil
Permar

Sallie Robey Permar

Wilburt C. Davison Distinguished Professor
Dr. Permar's work focuses on the development of vaccines to prevent vertical transmission of neonatal viral pathogens. She has utilized the nonhuman primate model of HIV/AIDS to characterize the virus-specific immune responses and virus evolution in breast milk and develop a maternal vaccine regimen for protection against breast milk transmission of HIV. In addition, Dr. Permar's lab has advanced the understanding of HIV-specific immune responses and virus evolution in vertically-transmitting an
Pollara

Justin Joseph Pollara

Associate Professor in Surgery
Sarzotti-Kelsoe

Marcella Sarzotti-Kelsoe

Research Professor of Immunology
Ongoing Applied Activities  •I direct a Global Quality Assurance Program, which I developed and pioneered here at Duke University, to oversee compliance with Good Clinical Laboratory Practice Guidelines in three HIV vaccine trial networks (CHAVI, CAVD, Duke HVTN, EQAPOL, Duke VTEU) involving domestic and international laboratory sites. •I also direct a Global Proficiency Testing Program for laboratories testing for neutralizing antibody function in individuals infected
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
Vandergrift

Nathan A. Vandergrift

Associate Professor in Medicine

John Franklin Whitesides

Assistant Professor in Medicine
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