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).
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.
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.
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: firstname.lastname@example.org
Received 20 September, 2017
Accepted 14 May, 2018
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