Details

Autor(en) / Beteiligte

• Zurawski, Gerard
• Zurawski, Sandra
• Flamar, Anne-Laure
• Richert, Laura
• Wagner, Ralf
• Tomaras, Georgia D
• Montefiori, David C
• Roederer, Mario
• Ferrari, Guido
• Lacabaratz, Christine
• Bonnabau, Henri
• Klucar, Peter
• Wang, Zhiqing
• Foulds, Kathryn E
• Kao, Shing-Fen
• Yates, Nicole L
• LaBranche, Celia
• Jacobs, Bertram L
• Kibler, Karen
• Asbach, Benedikt
• Kliche, Alexander
• Salazar, Andres
• Reed, Steve
• Self, Steve
• Gottardo, Raphael
• Galmin, Lindsey
• Weiss, Deborah
• Cristillo, Anthony
• Thiebaut, Rodolphe
• Pantaleo, Giuseppe
• Levy, Yves
• Wang, Shixia

Titel

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

Ist Teil von

• PloS one, 2016-04, Vol.11 (4), p.e0153484-e0153484

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.