title: Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.
abstract: A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.
authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.lastname: Vaccari
authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Department of Pathology, Case Western Reserve, Cleveland, Ohio, USA.
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.|Department of Biomedical and Clinical Sciences, 'L. Sacco' Hospital, University of Milan, Italy.
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authors.lastname: Schifanella
authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
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authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
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authors.affiliation: Duke Human Vaccine Institute, Durham, North Carolina, USA.
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authors.affiliation: Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: Georgia D
authors.initials: GD
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authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
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authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
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authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Boston, Massachusetts, USA.
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authors.affiliation: Department of Computer Science, Dartmouth College, Hanover, New Hampshire, USA.
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authors.affiliation: Department of Computer Science, Dartmouth College, Hanover, New Hampshire, USA.
authors.forename: Chris
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authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
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authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
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authors.affiliation: Immune Biology of Retroviral Infection Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
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authors.affiliation: Vaccine Research Center, US National Institutes of Health, Bethesda, Maryland, USA.
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authors.affiliation: Vaccine Research Center, US National Institutes of Health, Bethesda, Maryland, USA.
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authors.affiliation: Vaccine Research Center, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mitzi
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authors.affiliation: Karolinska Institute, Stockholm, Sweden.
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authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Karin
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authors.affiliation: Vaccine Research Center, US National Institutes of Health, Bethesda, Maryland, USA.
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authors.affiliation: Vaccine Research Center, US National Institutes of Health, Bethesda, Maryland, USA.
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authors.affiliation: California National Primate Research Center, University of California, Davis, California, USA.
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authors.affiliation: California National Primate Research Center, University of California, Davis, California, USA.
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authors.affiliation: University of California, Irvine School of Medicine, Irvine, California, USA.
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authors.affiliation: University of California, Irvine School of Medicine, Irvine, California, USA.
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Advanced Bioscience Laboratories, Rockville, Maryland, USA.
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authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
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authors.affiliation: Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
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authors.identifier: 0000-0002-8990-158X
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authors.lastname: Alter
authors.affiliation: Department of Pathology, Case Western Reserve, Cleveland, Ohio, USA.
authors.forename: Rafick-Pierre
authors.initials: RP
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authors.affiliation: Animal Models and Vaccine Section, National Cancer Institute, Bethesda, Maryland, USA.
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mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000534:Alum Compounds / Q000627:therapeutic use*; D000818:Animals; D007113:Immunity, Innate / Q000276:immunology; D018928:Immunity, Mucosal; D000071497:Immunogenicity, Vaccine; D007074:Immunoglobulin G / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D008214:Lymphocytes; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000276:immunology; D011897:Random Allocation; D018449:SAIDS Vaccines / Q000627:therapeutic use*; D015398:Signal Transduction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D059467:Transcriptome; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000627:therapeutic use*; D018631:ras Proteins / Q000276:immunology
chemical_list: C078788:ALVAC vaccine; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D007074:Immunoglobulin G; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C069623:gp120 protein, Simian immunodeficiency virus; C041524:aluminum sulfate; D018631:ras Proteins