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PLoS One. 2016 Apr 14;11(4):e0153484. doi: 10.1371/journal.pone.0153484. eCollection 2016.

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

Author information

1
Vaccine Research Institute, Université Paris-Est, Faculté de Médecine, INSERM U955, and Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert- Chenevier, service d'immunologie clinique, INRIA SISTM, Créteil, France.
2
Baylor Institute for Immunology Research and INSERM U955, Dallas, Texas, United States of America.
3
INSERM U897, INRIA SISTM, Université Bordeaux Segalen, Bordeaux, France.
4
Molecular Microbiology and Gene Therapy Unit, Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
5
Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
6
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
7
Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
8
School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
9
Oncovir, Washington, D.C., United States of America.
10
Infectious Disease Research Institute, Seattle, Washington, United States of America.
11
Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
12
Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America.
13
Centre Hospitalier Universitaire Vaudois, CH-101, Lausanne, Switzerland.

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.

PMID:
27077384
PMCID:
PMC4831750
DOI:
10.1371/journal.pone.0153484
[Indexed for MEDLINE]
Free PMC Article

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