Description

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

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.

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Title
  • Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques
Date Created
2016-04-14
Resource Type
  • Text
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    Identifier
    • Digital object identifier: 10.1371/journal.pone.0153484
    • Identifier Type
      International standard serial number
      Identifier Value
      1045-3830
    • Identifier Type
      International standard serial number
      Identifier Value
      1939-1560
    Note
    • The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153484

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    Zurawski, G., Zurawski, S., Flamar, A., Richert, L., Wagner, R., Tomaras, G. D., . . . Levy, Y. (2016). Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques. Plos One, 11(4). doi:10.1371/journal.pone.0153484

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