Document Detail

HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
MedLine Citation:
PMID:  22719248     Owner:  NLM     Status:  MEDLINE    
There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS)--only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log(10) lower (compared to 0.59 log(10) lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001) and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk.
Jennifer Mabuka; Ruth Nduati; Katherine Odem-Davis; Dylan Peterson; Julie Overbaugh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-14
Journal Detail:
Title:  PLoS pathogens     Volume:  8     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-11-09     Revised Date:  2013-08-30    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1002739     Citation Subset:  IM    
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
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MeSH Terms
Antibodies, Neutralizing / analysis*,  immunology
Antibody-Dependent Cell Cytotoxicity / immunology
Enzyme-Linked Immunosorbent Assay
HIV Antibodies / analysis*,  immunology
HIV Infections / immunology,  transmission*
HIV-1 / immunology
Immunoglobulin A / analysis
Immunoglobulin G / analysis
Milk, Human / chemistry,  immunology*
Randomized Controlled Trials as Topic
Viral Load
Grant Support
Reg. No./Substance:
0/Antibodies, Neutralizing; 0/HIV Antibodies; 0/Immunoglobulin A; 0/Immunoglobulin G

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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