1. Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.
- Author
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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, and Asbach, Benedikt
- Subjects
AIDS vaccines ,GLYCOPROTEINS ,RHESUS monkeys ,RECOMBINANT antibodies ,LEUCOCYTES - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2016
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