Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques

Gerard Zurawski (1) , Sandra Zurawski (2) , Anne-Laure Flamar (2) , Laura Richert (3, 1) , Ralf Wagner (4) , Georgia D. Tomaras (5) , David C. Montefiori (5) , Mario Roederer (6) , Guido Ferrari (5) , Christine Lacabaratz (7) , Henri Bonnabau (1) , Peter Klucar (2) , Zhiqing Wang (8, 2) , Kathryn E. Foulds (6) , Shing-Fen Kao (9) , Nicole L. Yates (10) , Celia Labranche (5) , Bertram L. Jacobs (11) , Karen Kibler (12) , Benedikt Asbach (4) , Alexander Kliche (4) , Andres Salazar (13) , Steve Reed (14) , Steve Self (15) , Raphael Gottardo (15) , Lindsey Galmin (16) , Deborah Weiss (17) , Anthony Cristillo (16) , Rodolphe Thiébaut (3) , Giuseppe Pantaleo (18) , Yves Levy (19, 20)

1 SISTM - Statistics In System biology and Translational Medicine
2 BIIR - Baylor Institute for Immunology Research
3 Epidémiologie et Biostatistique [Bordeaux]
4 IMHR - Institute of Medical Microbiology and Hygiene
5 Duke University Medical Center
6 VRC - Vaccine Research Center
7 IMRB - Institut Mondor de Recherche Biomédicale
8 VRI - Vaccine Research Institute [Créteil, France]
9 Department of Applied Mathematics, Chung Yuan Christian University
10 Rothamsted Research
11 Radboud University [Nijmegen]
12 ASU - Arizona State University [Tempe]
13 Oncovir [Washington]
14 IDRI - Infectious Disease Research Institute
15 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
16 ABL - Advanced Bioscience Laboratories
17 INRS-IAF - Institut Armand Frappier
18 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
19 INSERM - Institut National de la Santé et de la Recherche Médicale
20 Service d'immunologie clinique [Créteil]

Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant antibody for delivering Env directly to LOX-1-bearing antigen presenting cells, especially dendritic cells (DC). LOX-1, or 1ectin-like oxidized low-density lipoprotein (LDL) receptor-1, is expressed on various antigen presenting cells and endothelial cells, and is involved in promoting humoral immune responses. The anti-LOX-1 Env gp140 fusion protein was tested for priming immune responses and boosting responses in animals primed with replication competent NYVAC-KC Env gp140 vaccinia virus. Anti-LOX-1 Env gp140 vaccination elicited robust cellular and humoral responses when used for either priming or boosting immunity. Co-administration with Poly ICLC, a TLR3 agonist, was superior to GLA, a TLR4 agonist. Both CD4+ and CD8+ Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4+ T cells were multifunctional and directed to multiple epitopes. Serum IgG and IgA antibody responses induced by anti-LOX-1 Env gp140 against various gp140 domains were cross-reactive across HIV-1 clades; however, the sera neutralized only HIV-1 bearing sequences most similar to the clade C 96ZM651 Env gp140 carried by the anti-LOX-1 vehicle. These data, as well as the safety of this protein vaccine, justify further exploration of this DC-targeting vaccine approach for protective immunity against HIV-1.

Domaines: Vaccinologie

Gerard Zurawski, Sandra Zurawski, Anne-Laure Flamar, Laura Richert, Ralf Wagner, et al.. Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques. PLoS ONE, 2016, 11 (4), ⟨10.1371/journal.pone.0153484⟩. ⟨hal-01389087⟩