B Lymphocyte-Derived Humoral Immune Defenses in Breast Milk Transmission of the HIV-1

Bélec, Laurent; Kourtis, Athena P.

doi:10.1007/978-1-4614-2251-8_10

Cited by 7 publications

(8 citation statements)

References 177 publications

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“…The cofactors modulating HIV acquisition in the infant breastfed by HIV-infected mother have so far received until now relatively little attention [21], [23], [57], and few studies on this subject have been yet published [25], [26]. Our observations demonstrate for the first time the activation of HIV-specific humoral immunity by the intestinal mucosa of HIV-exposed children by breast-feeding.…”

Section: Discussionmentioning

confidence: 56%

“…The puzzling fact that the majority of breastfed infants born from HIV-infected mothers remain uninfected, even after several months of breast-feeding, constitutes one of the major paradoxes of HIV transmission via breast milk. The infrequent breast milk HIV transmission despite prolonged exposure suggests that anti-infective properties of breast milk may play a relevant protective role against infection of exposed children, and that natural and/or resistance to HIV in breastfed children could also be involved [21]. Finally, our observations raised acutely the issue of the putative roles of functionally active HIV-specific, intestinal antibodies in HIV transmission through breast-feeding.…”

Section: Discussionmentioning

confidence: 77%

“…The mechanism involved in this selective suppression of HIV-1-specific responses in the IgA isotype in mucosal secretions remains yet unresolved, and may be fundamental to understand how HIV is capable to be shed in corporeal fluid, i.e. to be produced by mucosal reservoirs despite the existence of mucosal immunity against the virus [21].…”

Section: Discussionmentioning

confidence: 99%

“…Induction of mucosal immunity against HIV following prolonged child exposure to infected breast milk is an attractive hypothesis [21], [23], [24]. Previous studies showed that HIV-1-uninfected babies exposed to HIV via breast-feeding may develop HIV-1-specific salivary IgA [25] as well as systemic HIV-specific CD8 cytotoxic immune responses [26].Overall, these observations suggest that the specific humoral and cellular immune defenses are activated in breastfed children.…”

Section: Introductionmentioning

confidence: 97%

“…The low frequency of breast-feeding acquisition suggests that anti-infective factors in breast-feeding HIV-infected mothers as well as in HIV exposed breastfed children are involved [20]. The fact that the majority of breastfed babies of HIV-infected mothers remain uninfected even after several months of breast-feeding constitutes one of the major paradoxes of HIV transmission via breast milk [21].…”

Section: Introductionmentioning

confidence: 99%

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Adaptive HIV-Specific B Cell-Derived Humoral Immune Defenses of the Intestinal Mucosa in Children Exposed to HIV via Breast-Feeding

et al. 2013

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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.

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