dc.contributor.author |
Pollara, Justin |
|
dc.contributor.author |
McGuire, Erin |
|
dc.contributor.author |
Fouda, Genevieve G |
|
dc.contributor.author |
Rountree, Wes |
|
dc.contributor.author |
Eudailey, Josh |
|
dc.contributor.author |
Overman, R Glenn |
|
dc.contributor.author |
Seaton, Kelly E |
|
dc.contributor.author |
Deal, Aaron |
|
dc.contributor.author |
Edwards, R Whitney |
|
dc.contributor.author |
Tegha, Gerald |
|
dc.contributor.author |
Kamwendo, Deborah |
|
dc.contributor.author |
Kumwenda, Jacob |
|
dc.contributor.author |
Nelson, Julie AE |
|
dc.contributor.author |
Liao, Hua-Xin |
|
dc.contributor.author |
Brinkley, Christie |
|
dc.contributor.author |
Denny, Thomas N |
|
dc.contributor.author |
Ochsenbauer, Christina |
|
dc.contributor.author |
Ellington, Sascha |
|
dc.contributor.author |
King, Caroline C |
|
dc.contributor.author |
Jamieson, Denise J |
|
dc.contributor.author |
van der Horst, Charles |
|
dc.contributor.author |
Kourtis, Athena P |
|
dc.contributor.author |
Tomaras, Georgia D |
|
dc.contributor.author |
Ferrari, Guido |
|
dc.contributor.author |
Permar, Sallie R |
|
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 |
https://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.publisher |
American Society for Microbiology |
|
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 |
|
duke.contributor.id |
Pollara, Justin|0300144 |
|
duke.contributor.id |
Fouda, Genevieve G|0420439 |
|
duke.contributor.id |
Liao, Hua-Xin|0107020 |
|
duke.contributor.id |
Denny, Thomas N|0400543 |
|
duke.contributor.id |
Tomaras, Georgia D|0204832 |
|
duke.contributor.id |
Ferrari, Guido|0108355 |
|
duke.contributor.id |
Permar, Sallie R|0554303 |
|
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 |
|
duke.contributor.orcid |
Tomaras, Georgia D|0000-0001-8076-1931 |
|
duke.contributor.orcid |
Ferrari, Guido|0000-0001-7747-3349 |
|