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A high mucosal blocking score is associated with HIV protection

Girard, Alexandrea; Rallón, Normab,c; Benito, José M.b,c; Jospin, Fabiennea; Rodriguez, Carmenc,d; Chanut, Blandinea; Benjelloun, Fahdf; Del Romero, Jorgec,d; Verrier, Bernarde; Lucht, Frédérica; Pin, Jean-Jacquesg; Genin, Christiana; Biasin, Marah,i; Clerici, Marioh,i; Paul, Stéphanea

doi: 10.1097/QAD.0000000000002099
BASIC SCIENCE
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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.

aGroupe Immunité des Muqueuses et Agents Pathogènes – GIMAP EA 3064, CIC 1408, Université de Saint-Etienne, Université de Lyon, Lyon, France

bIIS-Fundación Jiménez Díaz, UAM, Madrid

cHospital Universitario Rey Juan Carlos, Móstoles

dCentro Sanitario Sandoval, Madrid, Spain

eInstitut de Biologie et Chimie des Protéines, FRE3310/CNRS, Universités de Lyon, Lyon

fInstitut Pasteur, Paris

gDendritics, Lyon, France

hDepartment of Physiopathology Medical-Surgery and Transplantation, University of Milano

iDon C. Gnocchi Foundation ONLUS, IRCCS, Milano, Italy.

Correspondence to Stéphane Paul, Groupe Immunité des Muqueuses et Agents Pathogènes – GIMAP EA 3064, CIC 1408, Université de Saint-Etienne, Université de Lyon, Lyon, France. E-mail: stephane.paul@chu-st-etienne.fr

Received 20 September, 2017

Accepted 14 May, 2018

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Copyright © 2019 Wolters Kluwer Health, Inc.