A high mucosal blocking score is associated with HIV protection

Alexandre Girard, Norma Rallón, José M. Benito, Fabienne Jospin, Carmen Rodriguez, Blandine Chanut, Fahd Benjelloun, Jorge Del Romero, Bernard Verrier, Frédéric Lucht, Jean Jacques Pin, Christian Genin, Mara Biasin, Mario Clerici, Stéphane Paul

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Early steps of HIV infection are mediated by the binding of the envelope to mucosal receptors as α4β7 and the C-type lectins DC-SIGN and langerin. Previously Env-specific B-cell responses have been reported in highly exposed seronegative individuals (HESN). METHOD: Here, we studied gp120-specific antibodies ability to block HIV interaction with α4β7, DC-SIGN and/or langerinin HESN. New cell-based assays were developed to analyze whether antibodies that can alter gp120 binding to α4β7, DC-SIGN and/or langerin are induced in HESN. A mucosal blocking score (MBS) was defined based on the ability of antibodies to interfere with gp120/α4β7, gp120/DC-SIGN, and gp120/langerin binding. A new MBS was evaluated in a cohort of 86 HESN individuals and compared with HIV patients or HIV unexposed healthy individuals. RESULTS: Antibodies reducing gp120 binding to both α4β7 and DC-SIGN were present in HESN serum but also in mucosal secretions, whereas antibodies from HIV patients facilitated gp120 binding to DC-SIGN. Any correlation was observed between MBS and the capacity of antibodies to neutralize infection of α4β7 CD4 T cells with primary isolates. CONCLUSIONS: MBS is significantly associated with protection in HESN and might reflect altered HIV spreading to mucosal-associated lymphoid tissues.

Original languageEnglish
Pages (from-to)411-423
Number of pages13
JournalAIDS (London, England)
Volume33
Issue number3
DOIs
Publication statusPublished - Mar 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Girard, A., Rallón, N., Benito, J. M., Jospin, F., Rodriguez, C., Chanut, B., Benjelloun, F., Del Romero, J., Verrier, B., Lucht, F., Pin, J. J., Genin, C., Biasin, M., Clerici, M., & Paul, S. (2019). A high mucosal blocking score is associated with HIV protection. AIDS (London, England), 33(3), 411-423. https://doi.org/10.1097/QAD.0000000000002099