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Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.
- Source :
- PLoS ONE; 4/14/2016, Vol. 11 Issue 4, p1-23, 23p
- Publication Year :
- 2016
-
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<superscript>+</superscript> and CD8<superscript>+</superscript> Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4<superscript>+</superscript> 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]
- Subjects :
- AIDS vaccines
GLYCOPROTEINS
RHESUS monkeys
RECOMBINANT antibodies
LEUCOCYTES
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 114532364
- Full Text :
- https://doi.org/10.1371/journal.pone.0153484