Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission.
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 articleSubject
AIDS VaccinesAntibodies, 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
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http://hdl.handle.net/10161/12060Published Version (Please cite this version)
10.1172/JCI81593Publication Info
(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 http://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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Show full item recordScholars@Duke
S. Munir Alam
Professor in Medicine
Research Interests. Biophysical analysis of coreceptor modulation of TCR-MHC interactions.
One of our research interests is to study the molecular mechanisms of T cell recognition.
We have particular interest in understanding the trimolecular interactions between
membrane bound T cell receptor (TCR-CD3 complex) and its ligand, the peptide-MHC complex
(pMHC), and co-receptor molecules. We are using different biophysical approaches which
include surface plasmon resonance, isothermal titr
Santanu Kumar Datta
Assistant Professor in Medicine
BS, MBA, MS from Florida State University; PhD, University of North Carolina at Chapel
Hill. After earning his undergraduate degree in chemistry, Dr. Datta went on to earn
an MBA in finance and a masters degree in economics at Florida State University. He
then went to the University of North Carolina— Chapel Hill School of Public Health
to earn a doctorate in health policy and administration with a concentration in health
economics. Dr. Datta began his research career as an Associate in Re
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
Guido Ferrari
Associate Professor of 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
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.
Feng Gao
Professor of 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.
Barton Ford Haynes
Frederic M. Hanes 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
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
David Charles Montefiori
Professor of 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
Sallie Robey Permar
Professor of Pediatrics
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
Justin Joseph Pollara
Assistant Professor in Surgery
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
Georgia Doris Tomaras
Professor in Surgery
Research in the Tomaras Laboratory in the Duke Human Vaccine Institute and Departments
of Surgery, Immunology, and Molecular Genetics and Microbiology at Duke University
Medical Center, focuses on the identification of immune correlates of protection for
preventative vaccines and identification of the mechanisms responsible for potent
inhibition of human pathogens.
Nathan A. Vandergrift
Associate Professor in Medicine
John Franklin Whitesides
Assistant Professor in Medicine
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