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

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.

Detection of Zika virus in mouse mammary gland and breast milk

“…Human viruses with known clinically relevant risk of BMT are cytomegalovirus (CMV) [28] and HIV-1 [27, 29–31]. Although mastitis is a risk factor for BMT of both viruses, most cases of BMT occur in the absence of mastitis.…”

Human Breast Milk: From Food to Active Immune Response With Disease Protection in Infants and Mothers

“…Notably, breast milk samples and stool samples from HIV-negative and HIV-positive babies breastfed by their HIV-infected mothers, contained high levels of HIV-specific IgG. However, IgA antibodies were less frequent, and IgM are scarce ( 181 ). These antibodies, that specifically target gp120, purified from HIV-exposed breastfed infants, were able to inhibit HIV binding to HT29 cells and monocyte-derived macrophages ( 181 ).…”

“…However, IgA antibodies were less frequent, and IgM are scarce ( 181 ). These antibodies, that specifically target gp120, purified from HIV-exposed breastfed infants, were able to inhibit HIV binding to HT29 cells and monocyte-derived macrophages ( 181 ). Moreover, the intestinal mucosa of infant exposed to HIV by breastfeeding produces HIV-specific antibodies with inhibitory properties to HIV, showing the effect of prophylactic breastfeeding on immune responses of an infant against natural immunization with HIV ( 181 ).…”