title: Adaptive HIV-specific B cell-derived humoral immune defenses of the intestinal mucosa in children exposed to HIV via breast-feeding.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Couples 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).
  
  
  RESULTS
  The 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%.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Institut Pasteur de Bangui, Laboratoire des Rétrovirus-VIH, Bangui, Central African Republic. sandmoussa@hotmail.com
authors.forename: Sandrine
authors.initials: S
authors.lastname: Moussa
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Jean Chrysostome
authors.initials: JC
authors.lastname: Gody
authors.forename: Josiane
authors.initials: J
authors.lastname: Léal
authors.forename: Gérard
authors.initials: G
authors.lastname: Grésenguet
authors.forename: Alain
authors.initials: A
authors.lastname: Le Faou
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D001942:Breast Feeding; D002648:Child; D005243:Feces; D005260:Female; D015483:HIV Antibodies / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007223:Infant; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology; D007781:Lactoferrin / Q000378:metabolism; D008895:Milk, Human / Q000276:immunology; D012015:Reference Standards; D013045:Species Specificity; D055815:Young Adult
chemical_list: D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007140:Immunoglobulin Fab Fragments; D007781:Lactoferrin