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AIDS. 2019 Mar 1;33(3):411-423. doi: 10.1097/QAD.0000000000002099.

A high mucosal blocking score is associated with HIV protection.

Author information

1
Groupe Immunité des Muqueuses et Agents Pathogènes - GIMAP EA 3064, CIC 1408, Université de Saint-Etienne, Université de Lyon, Lyon, France.
2
IIS-Fundación Jiménez Díaz, UAM, Madrid.
3
Hospital Universitario Rey Juan Carlos, Móstoles.
4
Centro Sanitario Sandoval, Madrid, Spain.
5
Institut Pasteur, Paris.
6
Institut de Biologie et Chimie des Protéines, FRE3310/CNRS, Universités de Lyon, Lyon.
7
Dendritics, Lyon, France.
8
Department of Physiopathology Medical-Surgery and Transplantation, University of Milano.
9
Don C. Gnocchi Foundation ONLUS, IRCCS, Milano, Italy.

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.

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