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

Gerard Zurawski 1 Sandra Zurawski 1 Anne-Laure Flamar 1 Laura Richert 2, 3 Ralf Wagner 4 Georgia D. Tomaras 5 David C. Montefiori 6 Mario Roederer 7 Guido Ferrari 6 Christine Lacabaratz 8 Henri Bonnabau 3 Peter Klucar 1 Zhiqing Wang 9 Kathryn E. Foulds 7 Shing-Fen Kao 10 Nicole L. Yates 11 Celia Labranche 6 Bertram L. Jacobs 12 Karen Kibler 13 Benedikt Asbach 4 Alexander Kliche 4 Andres Salazar 14 Steve Reed 15 Steve Self 16 Raphael Gottardo 16 Lindsey Galmin 17, 18 Deborah Weiss 19 Anthony Cristillo 17 Rodolphe Thiebaut 20 Giuseppe Pantaleo 21 Yves Levy 22, 23
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.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2016, 11 (4), 〈10.1371/journal.pone.0153484〉
Liste complète des métadonnées

Littérature citée [43 références]  Voir  Masquer  Télécharger

https://hal.inria.fr/hal-01389087
Contributeur : Laura Richert <>
Soumis le : mardi 29 novembre 2016 - 13:37:13
Dernière modification le : vendredi 23 février 2018 - 17:12:11

Fichier

journal.pone.0153484.PDF
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Gerard Zurawski, Sandra Zurawski, Anne-Laure Flamar, Laura Richert, Ralf Wagner, et al.. Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques. PLoS ONE, Public Library of Science, 2016, 11 (4), 〈10.1371/journal.pone.0153484〉. 〈hal-01389087〉

Partager

Métriques

Consultations de la notice

232

Téléchargements de fichiers

52