HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies.
Abstract
Despite months of mucosal virus exposure, the majority of breastfed infants born to
HIV-infected mothers do not become infected, raising the possibility that immune factors
in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies
are present in the milk of HIV-infected mothers, but little is known about their virus-specific
functions. In this study, HIV Env-specific antibody binding, autologous and heterologous
virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were
measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is
the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher
in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV
gp120 IgG in milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet
the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous
virus neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001)
in milk were directly correlated with that in the systemic compartment but were 2
log units lower in magnitude. Autologous neutralization was rarely detected in milk.
Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding
IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r = 0.17 and
P = 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies
against a tier 1 virus (r = 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG
milk fractions had detectable neutralization. These results suggest that plasma-derived
IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity
in breast milk.
Type
Journal articleSubject
Antibodies, NeutralizingAntibody Formation
Antibody-Dependent Cell Cytotoxicity
Cross Reactions
Female
HIV Antibodies
HIV Infections
Humans
Immunoglobulin A
Immunoglobulin G
Milk, Human
Neutralization Tests
Plasma
env Gene Products, Human Immunodeficiency Virus
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https://hdl.handle.net/10161/14737Published Version (Please cite this version)
10.1128/JVI.05174-11Publication Info
Fouda, GG; Yates, NL; Pollara, J; Shen, X; Overman, GR; Mahlokozera, T; ... Immunology,
the Center for HIVAIDS Vaccine (2011). HIV-specific functional antibody responses in breast milk mirror those in plasma and
are primarily mediated by IgG antibodies. J Virol, 85(18). pp. 9555-9567. 10.1128/JVI.05174-11. Retrieved from https://hdl.handle.net/10161/14737.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
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
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.
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
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
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
Justin Joseph Pollara
Associate Professor in Surgery
Xiaoying Shen
Associate Professor in Surgery
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
Alphabetical list of authors with Scholars@Duke profiles.

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