HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.

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 cytot...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jennifer Mabuka, Ruth Nduati, Katherine Odem-Davis, Dylan Peterson, Julie Overbaugh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/83e5c3061c3741d7bfcc6fe3c6682880
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:83e5c3061c3741d7bfcc6fe3c6682880
record_format	dspace
spelling	oai:doaj.org-article:83e5c3061c3741d7bfcc6fe3c66828802021-11-18T06:04:19ZHIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.1553-73661553-737410.1371/journal.ppat.1002739https://doaj.org/article/83e5c3061c3741d7bfcc6fe3c66828802012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719248/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374There 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 MabukaRuth NduatiKatherine Odem-DavisDylan PetersonJulie OverbaughPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002739 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jennifer Mabuka Ruth Nduati Katherine Odem-Davis Dylan Peterson Julie Overbaugh HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
description	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.
format	article
author	Jennifer Mabuka Ruth Nduati Katherine Odem-Davis Dylan Peterson Julie Overbaugh
author_facet	Jennifer Mabuka Ruth Nduati Katherine Odem-Davis Dylan Peterson Julie Overbaugh
author_sort	Jennifer Mabuka
title	HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
title_short	HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
title_full	HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
title_fullStr	HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
title_full_unstemmed	HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
title_sort	hiv-specific antibodies capable of adcc are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/83e5c3061c3741d7bfcc6fe3c6682880
work_keys_str_mv	AT jennifermabuka hivspecificantibodiescapableofadccarecommoninbreastmilkandareassociatedwithreducedriskoftransmissioninwomenwithhighviralloads AT ruthnduati hivspecificantibodiescapableofadccarecommoninbreastmilkandareassociatedwithreducedriskoftransmissioninwomenwithhighviralloads AT katherineodemdavis hivspecificantibodiescapableofadccarecommoninbreastmilkandareassociatedwithreducedriskoftransmissioninwomenwithhighviralloads AT dylanpeterson hivspecificantibodiescapableofadccarecommoninbreastmilkandareassociatedwithreducedriskoftransmissioninwomenwithhighviralloads AT julieoverbaugh hivspecificantibodiescapableofadccarecommoninbreastmilkandareassociatedwithreducedriskoftransmissioninwomenwithhighviralloads
_version_	1718424614991822848

HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.

Ejemplares similares