A high mucosal blocking score is associated with HIV protection

被引：4

作者：

Girard, Alexandre ^{[1
]}

Rallon, Norma ^{[2
,3
]}

Benito, Jose M. ^{[2
,3
]}

Jospin, Fabienne ^{[1
]}

Rodriguez, Carmen ^{[3
,4
]}

Chanut, Blandine ^{[1
]}

Benjelloun, Fand ^{[6
]}

Del Romero, Jorge ^{[3
,4
]}

Verrier, Bernard ^{[5
]}

Lucht, Frederic ^{[1
]}

Pin, Jean-Jacques ^{[7
]}

Genin, Christian ^{[1
]}

Biasin, Mara ^{[8
,9
]}

Clerici, Mario ^{[8
,9
]}

Paul, Stephane ^{[1
]}

机构：

[1] Univ Lyon, Univ St Etienne, GIMAP, EA 3064,CIC 1408, Lyon, France

[2] UAM, IIS Fdn Jimenez Diaz, Madrid, Spain

[3] Hosp Univ Rey Juan Carlos, Mostoles, Spain

[4] Ctr Sanitario Sandoval, Madrid, Spain

[5] Univ Lyon, FRE3310, Inst Biol & Chim Prot, CNRS, Lyon, France

[6] Inst Pasteur, Paris, France

[7] Dendritics, Lyon, France

[8] Univ Milan, Dept Physiopathol Med Surg & Transplantat, Milan, Italy

[9] IRCCS, Don C Gnocchi Fdn ONLUS, Milan, Italy

来源：

AIDS | 2019年 / 33卷 / 03期

关键词：

alpha; 4; beta; 7; DC-SIGN; gp120; highly exposed seronegative; langerin; mucosal blocking score; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; EXPOSED SERONEGATIVE INDIVIDUALS; INTEGRIN ALPHA(4)BETA(7); DC-SIGN; DENDRITIC CELLS; ANTIBODIES; INFECTION; GP120; BINDING;

D O I：

10.1097/QAD.0000000000002099

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Early steps of HIV infection are mediated by the binding of the envelope to mucosal receptors as alpha 4 beta 7 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 alpha 4 beta 7, DC-SIGN and/or langerinin HESN. New cell-based assays were developed to analyze whether antibodies that can alter gp120 binding to alpha 4 beta 7, 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/alpha 4 beta 7, gp120/DC-SIGN, and gp120/langerin binding. A new MBS was evaluated in a cohort of 86 HESN individuals and compared with HIV thorn patients or HIV- unexposed healthy individuals. Results: Antibodies reducing gp120 binding to both alpha 4 beta 7 and DC-SIGN were present in HESN serum but also in mucosal secretions, whereas antibodies from HIV thorn patients facilitated gp120 binding to DC-SIGN. Any correlation was observed between MBS and the capacity of antibodies to neutralize infection of alpha 4 beta 7(+) 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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

引用

页码：411 / 423

页数：13