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Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

dc.contributor.author Brinkley, C
dc.contributor.author Deal, A
dc.contributor.author Denny, Thomas Norton
dc.contributor.author Edwards, RW
dc.contributor.author Ellington, S
dc.contributor.author Eudailey, Josh
dc.contributor.author Ferrari, Guido
dc.contributor.author Fouda, Genevieve
dc.contributor.author Jamieson, DJ
dc.contributor.author Kamwendo, D
dc.contributor.author King, CC
dc.contributor.author Kourtis, AP
dc.contributor.author Kumwenda, Jacob
dc.contributor.author Liao, Hua-Xin
dc.contributor.author McGuire, E
dc.contributor.author Nelson, JA
dc.contributor.author Ochsenbauer, C
dc.contributor.author Overman, RG
dc.contributor.author Permar, Sallie R
dc.contributor.author Pollara, Justin Joseph
dc.contributor.author Rountree, Wes
dc.contributor.author Seaton, Kelly
dc.contributor.author Tegha, G
dc.contributor.author Tomaras, Georgia Doris
dc.contributor.author van der Horst, C
dc.coverage.spatial United States
dc.date.accessioned 2016-06-01T14:43:59Z
dc.date.issued 2015-10
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/26202232
dc.identifier JVI.01560-15
dc.identifier.uri http://hdl.handle.net/10161/12061
dc.description.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.
dc.language eng
dc.relation.ispartof J Virol
dc.relation.isversionof 10.1128/JVI.01560-15
dc.subject Adult
dc.subject Antibodies, Neutralizing
dc.subject Antibody Specificity
dc.subject Antibody-Dependent Cell Cytotoxicity
dc.subject Breast Feeding
dc.subject Female
dc.subject HIV Antibodies
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Immunity, Mucosal
dc.subject Immunoglobulin A
dc.subject Immunoglobulin A, Secretory
dc.subject Immunoglobulin G
dc.subject Infant
dc.subject Infant, Newborn
dc.subject Infectious Disease Transmission, Vertical
dc.subject Malawi
dc.subject Milk, Human
dc.subject Models, Immunological
dc.subject Pregnancy
dc.subject Pregnancy Complications, Infectious
dc.subject Risk Factors
dc.subject Young Adult
dc.subject env Gene Products, Human Immunodeficiency Virus
dc.title Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/26202232
pubs.begin-page 9952
pubs.end-page 9961
pubs.issue 19
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Global Health Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Infectious Diseases
pubs.organisational-group School of Medicine
pubs.organisational-group Staff
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 89
dc.identifier.eissn 1098-5514


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