title: Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion.
abstract: Self-amplifying messenger RNA (mRNA) of positive-strand RNA viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. The SAM vaccine platform is based on a synthetic, self-amplifying mRNA delivered by a nonviral delivery system. The safety and immunogenicity of an HIV SAM vaccine encoding a clade C envelope glycoprotein formulated with a cationic nanoemulsion (CNE) delivery system was evaluated in rhesus macaques. The HIV SAM vaccine induced potent cellular immune responses that were greater in magnitude than those induced by self-amplifying mRNA packaged in a viral replicon particle (VRP) or by a recombinant HIV envelope protein formulated with MF59 adjuvant, anti-envelope binding (including anti-V1V2), and neutralizing antibody responses that exceeded those induced by the VRP vaccine. These studies provide the first evidence in nonhuman primates that HIV vaccination with a relatively low dose (50 µg) of formulated self-amplifying mRNA is safe and immunogenic.
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Willy M
authors.initials: WM
authors.lastname: Bogers
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Oostermeijer
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Davis
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Ulmer
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Brito
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Yen
authors.initials: Y
authors.lastname: Cu
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Kaustuv
authors.initials: K
authors.lastname: Banerjee
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Gillis R
authors.initials: GR
authors.lastname: Otten
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Brian
authors.initials: B
authors.lastname: Burke
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Antu
authors.initials: A
authors.lastname: Dey
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, United Kingdom.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke Human Vaccine Institute Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Celia
authors.initials: C
authors.lastname: Labranche
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke Human Vaccine Institute Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Barton
authors.initials: B
authors.lastname: Haynes
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Geall
authors.affiliation: Novartis Vacccines, Cambridge, Massachusetts.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D056704:Adaptive Immunity; D000818:Animals; D021461:Animals, Outbred Strains; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002412:Cations; D002478:Cells, Cultured; D004655:Emulsions; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D002412:Cations; D004655:Emulsions; D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1
keywords: HIV; T cells; antibodies; self-amplifying mRNA; vaccine