Zurawski, Gerard and Zurawski, Sandra and Flamar, Anne-Laure and Richert, Laura and Wagner, Ralf and Tomaras, Georgia D. and Montefiori, David C. and Roederer, Mario and Ferrari, Guido and Lacabaratz, Christine and Bonnabau, Henri and Klucar, Peter and Wang, Zhiqing and Foulds, Kathryn E. and Kao, Shing-Fen and Yates, Nicole L. and LaBranche, Celia and Jacobs, Bertram L. and Kibler, Karen and Asbach, Benedikt and Kliche, Alexander and Salazar, Andres and Reed, Steve and Self, Steve and Gottardo, Raphael and Galmin, Lindsey and Weiss, Deborah and Cristillo, Anthony and Thiebaut, Rodolphe and Pantaleo, Giuseppe and Levy, Yves (2016) Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques. PLOS ONE, 11 (4): e0153484. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELL RESPONSES; NONHUMAN-PRIMATES; DENDRITIC CELLS; EFFICACY TRIAL; IMMUNOLOGICAL CHARACTERIZATION; LANGERHANS CELLS; VACCINIA VIRUS; ANTIBODIES; PROTEIN; ANTIGENS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Apr 2019 07:31 |
| Last Modified: | 05 Apr 2019 07:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3077 |
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