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), 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.
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
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,
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
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
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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