title: Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.
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.
authors.affiliation: 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.|Baylor Institute for Immunology Research and INSERM U955, Dallas, Texas, United States of America.
authors.forename: Gerard
authors.identifier: http://orcid.org/0000-0002-0168-3523
authors.initials: G
authors.lastname: Zurawski
authors.affiliation: 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.|Baylor Institute for Immunology Research and INSERM U955, Dallas, Texas, United States of America.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.affiliation: 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.|Baylor Institute for Immunology Research and INSERM U955, Dallas, Texas, United States of America.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Flamar
authors.affiliation: INSERM U897, INRIA SISTM, Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Richert
authors.affiliation: Molecular Microbiology and Gene Therapy Unit, Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.|Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.|Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Lacabaratz
authors.affiliation: INSERM U897, INRIA SISTM, Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Bonnabau
authors.affiliation: 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.|Baylor Institute for Immunology Research and INSERM U955, Dallas, Texas, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Klucar
authors.affiliation: 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.|Baylor Institute for Immunology Research and INSERM U955, Dallas, Texas, United States of America.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Foulds
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Shing-Fen
authors.initials: SF
authors.lastname: Kao
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Yates
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Jacobs
authors.affiliation: School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Kibler
authors.affiliation: Molecular Microbiology and Gene Therapy Unit, Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Asbach
authors.affiliation: Molecular Microbiology and Gene Therapy Unit, Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kliche
authors.affiliation: Oncovir, Washington, D.C., United States of America.
authors.forename: Andres
authors.initials: A
authors.lastname: Salazar
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, United States of America.
authors.forename: Steve
authors.initials: S
authors.lastname: Reed
authors.affiliation: Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Steve
authors.initials: S
authors.lastname: Self
authors.affiliation: Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.affiliation: Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Galmin
authors.affiliation: Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America.
authors.forename: Deborah
authors.initials: D
authors.lastname: Weiss
authors.affiliation: Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Cristillo
authors.affiliation: INSERM U897, INRIA SISTM, Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiebaut
authors.affiliation: Centre Hospitalier Universitaire Vaudois, CH-101, Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.affiliation: 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.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000276:immunology; D051127:Scavenger Receptors, Class E / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; C495137:OLR1 protein, human; D011993:Recombinant Fusion Proteins; D051127:Scavenger Receptors, Class E; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1