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2013;8 (5): e63408.

Adaptive HIV-specific B cell-derived humoral immune defenses of the intestinal mucosa in children exposed to HIV via breast-feeding.

Sandrine Moussa, Mohammad-Ali Jenabian, Jean Chrysostome Gody, Josiane Léal, Gérard Grésenguet, Alain Le Faou, Laurent Bélec
Author Information
  1. Sandrine Moussa: Institut Pasteur de Bangui, Laboratoire des Rétrovirus-VIH, Bangui, Central African Republic. sandmoussa@hotmail.com
PMID: 23704905 DOI: 10.1371/journal.pone.0063408

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.

References

  1. Adv Exp Med Biol. 2012;743:121-37 [PMID: 22454346]
  2. Pediatrics. 2003 Oct;112(4):e289 [PMID: 14523214]
  3. AIDS. 1997 Nov;11(13):1627-33 [PMID: 9365768]
  4. Lancet. 2007 Mar 31;369(9567):1107-16 [PMID: 17398310]
  5. Lancet. 2004 Nov 20-26;364(9448):1865-71 [PMID: 15555666]
  6. J Pediatr. 2006 Nov;149(5):611-6 [PMID: 17095329]
  7. AIDS Res Hum Retroviruses. 2012 Jan;28(1):87-94 [PMID: 21599597]
  8. Haematologica. 1995 May-Jun;80(3):252-67 [PMID: 7672721]
  9. J Infect Dis. 2003 Mar 1;187(5):736-40 [PMID: 12599046]
  10. Virology. 2007 Jul 5;363(2):256-60 [PMID: 17335864]
  11. Immunol Cell Biol. 1997 Oct;75(5):419-29 [PMID: 9429889]
  12. AIDS Res Hum Retroviruses. 2011 May;27(5):469-86 [PMID: 21091128]
  13. Gut. 2002 May;50(5):608-14 [PMID: 11950804]
  14. Arch Dis Child. 1980 Jun;55(6):417-21 [PMID: 7002055]
  15. J Pediatr. 1988 Dec;113(6):1039-41 [PMID: 3057158]
  16. Ann Allergy. 1984 Dec;53(6 Pt 2):576-82 [PMID: 6391286]
  17. AIDS Res Hum Retroviruses. 2004 Feb;20(2):219-26 [PMID: 15018710]
  18. Vaccine. 2003 Jul 28;21(24):3382-8 [PMID: 12850345]
  19. J Transl Med. 2007 Jun 12;5:28 [PMID: 17565674]
  20. J Hum Lact. 2011 May;27(2):171-86 [PMID: 21678611]
  21. N Engl J Med. 1983 Aug 25;309(8):453-8 [PMID: 6224088]
  22. Pediatrics. 1990 Jun;85(6):1022-6 [PMID: 2339025]
  23. Clin Exp Immunol. 2008 Jul;153(1):37-43 [PMID: 18505437]
  24. N Engl J Med. 2010 Jun 17;362(24):2271-81 [PMID: 20554982]
  25. Pediatr Infect Dis J. 1994 Jul;13(7):603-8 [PMID: 7970947]
  26. AIDS Res Hum Retroviruses. 2010 Sep;26(9):967-75 [PMID: 20718630]
  27. Lancet. 1993 Apr 10;341(8850):914-8 [PMID: 8096264]
  28. Am J Obstet Gynecol. 2007 Sep;197(3 Suppl):S64-71 [PMID: 17825652]
  29. J Immunol. 2006 Oct 15;177(8):5540-9 [PMID: 17015741]
  30. AIDS Res Hum Retroviruses. 1999 Oct 10;15(15):1365-76 [PMID: 10515152]
  31. Pediatr Infect Dis J. 1993 Aug;12(8):664-71 [PMID: 8414780]
  32. J Clin Invest. 1984 Aug;74(2):525-35 [PMID: 6746905]
  33. Lancet. 1997 Apr 12;349(9058):1054-9 [PMID: 9107243]
  34. Ann N Y Acad Sci. 2000 Nov;918:122-7 [PMID: 11131695]
  35. J Infect Dis. 1997 Feb;175(2):265-71 [PMID: 9203646]
  36. J Virol. 1998 Apr;72(4):2708-14 [PMID: 9525588]
  37. Clin Chem Lab Med. 2003 Feb;41(2):134-8 [PMID: 12666997]
  38. J Virol. 2011 Sep;85(18):9555-67 [PMID: 21734046]
  39. AIDS Res Hum Retroviruses. 2004 Jun;20(6):621-9 [PMID: 15242538]
  40. J Infect Dis. 2000 Feb;181(2):532-9 [PMID: 10669336]
  41. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):603-8 [PMID: 11209057]
  42. AIDS. 2008 Jul 31;22(12):1461-2 [PMID: 18614869]
  43. Nutr Rev. 1999 May;57(5 Pt 1):146-53 [PMID: 10391017]
  44. N Engl J Med. 2010 Jun 17;362(24):2282-94 [PMID: 20554983]
  45. J Infect Dis. 1994 Nov;170(5):1134-40 [PMID: 7963705]
  46. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Jul 1;15(3):185-91 [PMID: 9257652]
  47. J Infect Dis. 1998 Jan;177(1):34-9 [PMID: 9419167]
  48. Clin Exp Immunol. 2003 Dec;134(3):367-77 [PMID: 14632739]
  49. J Virol. 1992 Jan;66(1):580-5 [PMID: 1727501]
  50. AIDS. 1999 Jul 30;13(11):1323-31 [PMID: 10449284]
  51. Clin Vaccine Immunol. 2008 May;15(5):872-84 [PMID: 18353923]
  52. AIDS Res Hum Retroviruses. 2002 Nov 20;18(17):1291-300 [PMID: 12487817]
  53. Trop Med Int Health. 2009 Mar;14(3):276-87 [PMID: 19171011]
  54. Pediatr Infect Dis J. 2005 Nov;24(11):993-7 [PMID: 16282936]
  55. J Infect Dis. 1989 Sep;160(3):385-91 [PMID: 2760496]
  56. Crit Rev Immunol. 2009;29(5):369-77 [PMID: 20001886]
  57. JAMA. 2006 Aug 16;296(7):794-805 [PMID: 16905785]
  58. J Infect Dis. 2009 Mar 15;199(6):889-98 [PMID: 19434932]
  59. Drugs Today (Barc). 2012 Feb;48(2):149-61 [PMID: 22384454]
  60. Clin Infect Dis. 2011 Mar 15;52(6):819-25 [PMID: 21367736]
  61. J Leukoc Biol. 2007 Mar;81(3):642-53 [PMID: 16971466]
  62. J Nutr. 2011 May;141(5):957-63 [PMID: 21411606]
  63. Acta Paediatr Scand. 1982 Nov;71(6):979-85 [PMID: 6818832]
  64. Nat Rev Microbiol. 2006 Apr;4(4):312-7 [PMID: 16541138]
  65. AIDS Res Ther. 2008 Jun 03;5:10 [PMID: 18522743]
  66. Scand J Immunol. 1995 Aug;42(2):269-74 [PMID: 7631160]
  67. J Acquir Immune Defic Syndr (1988). 1992;5(1):65-9 [PMID: 1738088]
  68. Clin Immunol. 2000 Oct;97(1):59-68 [PMID: 10998318]
  69. AIDS. 2007 Aug 20;21(13):1747-52 [PMID: 17690573]
  70. AIDS Res Hum Retroviruses. 2010 Nov;26(11):1247-8 [PMID: 20939688]
  71. PLoS Pathog. 2012;8(4):e1002599 [PMID: 22532797]
  72. Pediatr Res. 1990 Mar;27(3):252-5 [PMID: 2320391]
  73. J Intern Med. 2007 Jul;262(1):44-58 [PMID: 17598814]
  74. J Virol. 2010 Aug;84(16):8209-18 [PMID: 20519381]
  75. AIDS. 2005 Nov 18;19(17):1947-55 [PMID: 16260900]
  76. J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):196-202 [PMID: 14722454]
  77. JAMA. 1999 Aug 25;282(8):744-9 [PMID: 10463709]
  78. J Immunol. 2007 Sep 1;179(5):3362-70 [PMID: 17709553]
  79. J Infect Dis. 1996 Oct;174(4):722-6 [PMID: 8843208]
  80. J Virol. 1992 Apr;66(4):2232-9 [PMID: 1548759]
  81. Open Virol J. 2011;5:27-34 [PMID: 21660187]
  82. AIDS Res Hum Retroviruses. 1994 Apr;10(4):359-69 [PMID: 7520721]
  83. N Engl J Med. 2008 Jul 10;359(2):119-29 [PMID: 18525035]
  84. J Leukoc Biol. 2003 Nov;74(5):642-9 [PMID: 12960227]
  85. J Acquir Immune Defic Syndr. 2007 Aug 1;45(4):380-8 [PMID: 17468666]
  86. J Infect Dis. 2010 Nov 1;202 Suppl 3:S329-32 [PMID: 20887219]
  87. AIDS. 1999 Jun 18;13(9):1133-8 [PMID: 10397545]
  88. Virology. 2008 Jan 20;370(2):246-54 [PMID: 17920650]
  89. J Acquir Immune Defic Syndr. 2002 Jun 1;30(2):230-9 [PMID: 12045686]
  90. Ann N Y Acad Sci. 1995 May 31;754:97-107 [PMID: 7625685]
  91. J Virol. 2001 Jun;75(11):5370-4 [PMID: 11333919]
  92. Rev Med Virol. 2007 Nov-Dec;17(6):381-403 [PMID: 17542053]
  93. J Med Primatol. 1995 Feb;24(2):53-60 [PMID: 8613973]
  94. Adv Exp Med Biol. 2012;743:139-60 [PMID: 22454347]
  95. J Immunol. 2002 Sep 15;169(6):3301-6 [PMID: 12218150]
  96. J Immunol. 2009 May 15;182(10):5914-8 [PMID: 19414742]
  97. J Acquir Immune Defic Syndr. 2008 Dec 15;49(5):566-9 [PMID: 19202461]
  98. J Infect Dis. 2001 Dec 1;184(11):1412-22 [PMID: 11709783]
  99. Curr HIV Res. 2007 Nov;5(6):588-93 [PMID: 18045115]
  100. Lancet Infect Dis. 2003 Dec;3(12):786-93 [PMID: 14652204]
  101. J Virol. 2012 Mar;86(5):2556-70 [PMID: 22205732]
  102. AIDS Res Hum Retroviruses. 2004 Sep;20(9):972-88 [PMID: 15585085]
  103. AIDS. 1995 Jan;9(1):93-4 [PMID: 7893449]
  104. J Infect Dis. 1995 Sep;172(3):691-7 [PMID: 7658060]
  105. J Virol. 2011 Mar;85(6):2751-63 [PMID: 21191008]
  106. Blood. 2004 Mar 15;103(6):2180-6 [PMID: 14604962]
  107. J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):425-8 [PMID: 20562721]

MeSH Term

Adaptive Immunity
Adult
B-Lymphocytes
Breast Feeding
Child
Feces
Female
HIV Antibodies
HIV Envelope Protein gp160
HIV Infections
HIV-1
Humans
Immunity, Humoral
Immunoglobulin Fab Fragments
Infant
Intestinal Mucosa
Lactoferrin
Milk, Human
Reference Standards
Species Specificity
Young Adult

Chemicals

HIV Antibodies
HIV Envelope Protein gp160
Immunoglobulin Fab Fragments
Lactoferrin
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

Created with Highcharts 10.0.0antibodieschildrenHIV-specificHIVexposedbreast-feedingbreastfedHIV-infectedIgAIgGstoolsMDMBcell-derivedmothersbabiesIgMmilkattachmentHIV-exposedintestinalmucosaimmunedefensesviaHIV-negativeanti-gp160purifiedinfectionHT29cellslevelsindicatingsamplesHIV-1JRCSFBACKGROUND:evaluatedwhethergastro-intestinaltractactivatedproducecontinuouslyMETHODS:CouplesHIV-1-infectedn = 14nonn = 8n = 6healthyn = 10controlsprospectivelyincludedComplexePédiatriqueBanguiCentralAfricanRepublicImmunoglobulinsmother'squantifiedELISAImmunoaffinitycharacterizedfunctionallyregardingcapacityreduceand/orR5-X4-tropicHIV-1strainshumancolorectalepitheliallinemonocyte-derived-macrophagesRESULTS:totalincreasedactivationmucosalimmunityBreastwellstoolcontainedhighmainlylessfrequentlyrarelyRelativeratiosexcretionreferencelactoferrincalculatedlargelysuperior1activeproductionAntibodiesgp160pooledinhibitedHIV-1NDK63%77%40%93%CONCLUSIONS:producesharbouringvitromajorfunctionalpropertiesobservationslayconceptualbasisdesignprophylacticvaccineAdaptivehumoral

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