Abstract
BackgroundWe evaluated whether B cell-derived immune defenses of the gastro-intestinal tract are activated to produce HIV-specific antibodies in children continuously exposed to HIV via breast-feeding.MethodsCouples of HIV-1-infected mothers (n = 14) and their breastfed non HIV-infected (n = 8) and HIV-infected (n = 6) babies, and healthy HIV-negative mothers and breastfed babies (n = 10) as controls, were prospectively included at the Complexe Pédiatrique of Bangui, Central African Republic. Immunoglobulins (IgA, IgG and IgM) and anti-gp160 antibodies from mother’s milk and stools of breastfed children were quantified by ELISA. Immunoaffinity purified anti-gp160 antibodies were characterized functionally regarding their capacity to reduce attachment and/or infection of R5- and X4- tropic HIV-1 strains on human colorectal epithelial HT29 cells line or monocyte-derived-macrophages (MDM).ResultsThe levels of total IgA and IgG were increased in milk of HIV-infected mothers and stools of HIV-exposed children, indicating the activation of B cell-derived mucosal immunity. Breast milk samples as well as stool samples from HIV-negative and HIV-infected babies exposed to HIV by breast-feeding, contained high levels of HIV-specific antibodies, mainly IgG antibodies, less frequently IgA antibodies, and rarely IgM antibodies. Relative ratios of excretion by reference to lactoferrin calculated for HIV-specific IgA, IgG and IgM in stools of HIV-exposed children were largely superior to 1, indicating active production of HIV-specific antibodies by the intestinal mucosa. Antibodies to gp160 purified from pooled stools of HIV-exposed breastfed children inhibited the attachment of HIV-1NDK on HT29 cells by 63% and on MDM by 77%, and the attachment of HIV-1JRCSF on MDM by 40%; and the infection of MDM by HIV-1JRCSF by 93%.ConclusionsThe intestinal mucosa of children exposed to HIV by breast-feeding produces HIV-specific antibodies harbouring in vitro major functional properties against HIV. These observations lay the conceptual basis for the design of a prophylactic vaccine against HIV in exposed children.
Highlights
The UNAIDS estimated that more than 330,000 (280,000– 380,000) children were newly infected by human immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission (MTCT) worldwide in 2011, with the majority (.90%) occurring in sub-Saharan Africa [1]
The aim of the present study was to evaluate whether B cellderived immune defenses of gastro-intestinal tract are activated to produce HIV-specific antibodies in breastfed children continuously exposed to HIV via breast-feeding
Inclusion of Mothers and their Breastfed Babies Couples of HIV-1-infected mothers and their breastfed babies were consecutively recruited at the Complexe Pediatrique, the principal health care clinic for HIV-infected children held in Bangui, the capital city of the Central African Republic [27,28,29].The study was formally approved by the Scientific Committee of the Facultedes Sciences de la Sante (‘‘FACSS’’) of Bangui, constituting the National Ethical Committee
Summary
The UNAIDS estimated that more than 330,000 (280,000– 380,000) children were newly infected by human immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission (MTCT) worldwide in 2011, with the majority (.90%) occurring in sub-Saharan Africa [1]. While studies of maternal or infant antiretroviral therapy during the period of breast-feeding have shown substantial potential for reduction of infant HIV infections [11,12,13,14], postnatal virus transmissions may continue to occur even in the setting of optimal antiretroviral prophylaxis [15].development of immunologic strategies to reduce HIV transmission via breast milk remains important for improving survival of babies born to HIV-infected mothers in the developing world. Consumption of 0.5–1.0 liter of breast milk daily provides continuous exposure to potentially infectious virus through the oral cavity and the gastrointestinal mucosa. Less than 10% of babies born to HIV-infected women and breastfed during the first 6 months of life become infected postnatal [19], indicating low efficiency of breast milk transmission which is in contrast with the daily exposure to high amount of infectious viral particles. We evaluated whether B cell-derived immune defenses of the gastro-intestinal tract are activated to produce HIV-specific antibodies in children continuously exposed to HIV via breast-feeding
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