Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.
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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.
Antibody-Dependent Cell Cytotoxicity
Immunoglobulin A, Secretory
Infectious Disease Transmission, Vertical
Pregnancy Complications, Infectious
env Gene Products, Human Immunodeficiency Virus
Published Version (Please cite this version)10.1128/JVI.01560-15
Publication InfoBrinkley, C; Deal, A; Denny, Thomas Norton; Edwards, RW; Ellington, S; Eudailey, Josh; ... van der Horst, C (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 http://hdl.handle.net/10161/12061.
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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
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
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.
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
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
Assistant Professor in Surgery
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.
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