Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.
Abstract
UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where
replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout
breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally,
even in the absence of maternal antiretroviral therapy. This suggests that immune
factors in breast milk of HIV-1-infected mothers help to limit vertical transmission.
We compared the HIV-1 envelope-specific breast milk and plasma antibody responses
of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in
the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study
using multivariable logistic regression modeling. We found no association between
milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity,
or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the
envelope-specific breast milk and plasma IgA responses also did not reach significance
in predicting postnatal transmission risk in the primary model after correction for
multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies
demonstrated that the magnitudes of breast milk total and secretory IgA responses
against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced
postnatal transmission risk. These results suggest a protective role for mucosal HIV-1
envelope-specific IgA responses in the context of postnatal virus transmission. This
finding supports further investigations into the mechanisms by which mucosal IgA reduces
risk of HIV-1 transmission via breast milk and into immune interventions aimed at
enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly
exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting
that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission.
We compared the antibody responses in plasma and breast milk of HIV-1-transmitting
and -nontransmitting mothers to identify responses that correlated with reduced risk
of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG
antibody responses were associated with risk of HIV-1 transmission. In contrast, the
magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope
proteins were associated with reduced risk of postnatal HIV-1 transmission. The results
of this study support further investigations of the mechanisms by which mucosal IgA
may reduce the risk of HIV-1 transmission via breastfeeding and the development of
strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child
HIV transmission and promote an HIV-free generation.
Type
Journal articleSubject
AdultAntibodies, Neutralizing
Antibody Specificity
Antibody-Dependent Cell Cytotoxicity
Breast Feeding
Female
HIV Antibodies
HIV Infections
HIV-1
Humans
Immunity, Mucosal
Immunoglobulin A
Immunoglobulin A, Secretory
Immunoglobulin G
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical
Malawi
Milk, Human
Models, Immunological
Pregnancy
Pregnancy Complications, Infectious
Risk Factors
Young Adult
env Gene Products, Human Immunodeficiency Virus
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https://hdl.handle.net/10161/12061Published Version (Please cite this version)
10.1128/JVI.01560-15Publication Info
Pollara, Justin; McGuire, Erin; Fouda, Genevieve G; Rountree, Wes; Eudailey, Josh;
Overman, R Glenn; ... Permar, Sallie R (2015). Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk
of Postnatal Mother-to-Child Transmission of HIV-1. J Virol, 89(19). pp. 9952-9961. 10.1128/JVI.01560-15. Retrieved from https://hdl.handle.net/10161/12061.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.
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.
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
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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