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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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https://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 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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Show full item recordScholars@Duke
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
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
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 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.
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
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
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
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,
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 Integrative Immunobiology 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 in
Sallie Robey Permar
Adjunct Professor in the Department of Pathology
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
Associate Professor in Surgery
Dr. Justin Pollara is a member of the Duke Human Vaccine Institute and the Duke Center
for Human Systems Immunology, and is Associate Director of the Duke Center for AIDS
Research (CFAR) Developmental Core. He received his PhD from North Carolina State
University and completed his postdoctoral training as a recipient of the Duke NIH
Interdisciplinary Research Training Program in AIDS (IRTPA) T32 award in the laboratory
of Dr. Guido Ferrari. He joined the faculty of the Duke Department of Surg
Marcella Sarzotti-Kelsoe
Research Professor of Integrative Immunobiology
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
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
Nathan A. Vandergrift
Associate Professor in Medicine
John Franklin Whitesides
Assistant Professor in Medicine
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