; 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 | Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | PLOS ONE | ||||
| Publisher: | PLOS | ||||
| Place of Publication: | SAN FRANCISCO | ||||
| Volume: | 11 | ||||
| Number of Issue or Book Chapter: | 4 | ||||
| Page Range: | e0153484 | ||||
| Date: | 2016 | ||||
| Institutions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene | ||||
| Identification Number: |
| ||||
| Keywords: | T-CELL RESPONSES; NONHUMAN-PRIMATES; DENDRITIC CELLS; EFFICACY TRIAL; IMMUNOLOGICAL CHARACTERIZATION; LANGERHANS CELLS; VACCINIA VIRUS; ANTIBODIES; PROTEIN; ANTIGENS; | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 42290 |

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 ...

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.
Metadata last modified: 17 Mar 2020 11:27
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