PLoS ONE (2016-01-01)

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

  • Gerard Zurawski,
  • Sandra Zurawski,
  • Anne-Laure Flamar,
  • Laura Richert,
  • Ralf Wagner,
  • Georgia D Tomaras,
  • David C Montefiori,
  • Mario Roederer,
  • Guido Ferrari,
  • Christine Lacabaratz,
  • Henri Bonnabau,
  • Peter Klucar,
  • Zhiqing Wang,
  • Kathryn E Foulds,
  • Shing-Fen Kao,
  • Nicole L Yates,
  • Celia LaBranche,
  • Bertram L Jacobs,
  • Karen Kibler,
  • Benedikt Asbach,
  • Alexander Kliche,
  • Andres Salazar,
  • Steve Reed,
  • Steve Self,
  • Raphael Gottardo,
  • Lindsey Galmin,
  • Deborah Weiss,
  • Anthony Cristillo,
  • Rodolphe Thiebaut,
  • Giuseppe Pantaleo,
  • Yves Levy

DOI
https://doi.org/10.1371/journal.pone.0153484
Journal volume & issue
Vol. 11, no. 4
p. e0153484

Abstract

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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.