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

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Serval ID
serval:BIB_980FC2E7134A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.
Journal
Plos One
Author(s)
Zurawski G., Zurawski S., Flamar A.L., Richert L., Wagner R., Tomaras G.D., Montefiori D.C., Roederer M., Ferrari G., Lacabaratz C., Bonnabau H., Klucar P., Wang Z., Foulds K.E., Kao S.F., Yates N.L., LaBranche C., Jacobs B.L., Kibler K., Asbach B., Kliche A., Salazar A., Reed S., Self S., Gottardo R., Galmin L., Weiss D., Cristillo A., Thiebaut R., Pantaleo G., Levy Y.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
11
Number
4
Pages
e0153484
Language
english
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.
Keywords
AIDS Vaccines/immunology, Animals, Antibodies, Monoclonal, Humanized/immunology, Antibodies, Viral/immunology, Antibody Specificity, HIV-1/immunology, Humans, Macaca mulatta, Male, Mice, Recombinant Fusion Proteins/immunology, Scavenger Receptors, Class E/immunology, T-Lymphocytes/immunology, env Gene Products, Human Immunodeficiency Virus/immunology
Pubmed
Web of science
Open Access
Yes
Create date
03/05/2016 18:04
Last modification date
20/08/2019 15:59
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