title: Safety and immunogenicity of an adjuvanted protein therapeutic HIV-1 vaccine in subjects with HIV-1 infection: a randomised placebo-controlled study.
abstract: The human immunodeficiency virus type-1 (HIV-1) vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional CD4(+) T-cell responses in HIV-1-seronegative volunteers. This placebo-controlled study evaluated two doses of F4/AS01 1-month apart in antiretroviral treatment (ART)-experienced and ART-naïve HIV-1-infected subjects (1:1 randomisation in each cohort). Safety, HIV-1-specific CD4(+) and CD8(+) T-cell responses, absolute CD4(+) T-cell counts and HIV-1 viral load were monitored for 12 months post-vaccination. Reactogenicity was clinically acceptable and no vaccine-related serious adverse events were reported. The frequency of HIV-1-specific CD4(+) T-cells 2 weeks post-dose 2 was significantly higher in the vaccine group than in the placebo group in both cohorts (p<0.05). Vaccine-induced HIV-1-specific CD4(+) T-cells exhibited a polyfunctional phenotype, expressing at least CD40L and IL-2. No increase in HIV-1-specific CD8(+) T-cells or change in CD8(+) T-cell activation marker expression profile was detected. Absolute CD4(+) T-cell counts were variable over time in both cohorts. Viral load remained suppressed in ART-experienced subjects. In ART-naïve subjects, a transient reduction in viral load from baseline was observed 2 weeks after the second F4/AS01 dose, which was concurrent with a higher frequency of HIV-1-specific CD4(+) T-cells expressing at least IL-2 in this cohort. In conclusion, F4/AS01 showed a clinically acceptable reactogenicity and safety profile, and induced polyfunctional HIV-1-specific CD4(+) T-cell responses in ART-experienced and ART-naïve subjects. These findings support further clinical investigation of F4/AS01 as a potential HIV-1 vaccine for therapeutic use in individuals with HIV-1 infection.
authors.affiliation: Department of Internal Medicine III, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. Electronic address: Thomas.Harrer@uk-erlangen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Harrer
authors.affiliation: ifi-Institut für interdisziplinäre Medizin/Haus K, Asklepios Klinik St. Georg, Lohmühlenstr. 5, 20099 Hamburg, Germany. Electronic address: plettenberg@ifi-medizin.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Plettenberg
authors.affiliation: EPIMED/Vivantes Auguste-Viktoria-Klinikum, Rubensstr. 125, 12157 Berlin, Germany. Electronic address: keikawus.arasteh@vivantes.de.
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arastéh
authors.affiliation: Infectious Diseases Unit, University Medical Centre, Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: v.lunzen@uke.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Lunzen
authors.affiliation: Klinik I für Innere Medizin, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany. Electronic address: g.faetkenheuer@uni-koeln.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: MUC Research GmbH, Karlsplatz 8, 80335 Munich, Germany. Electronic address: info@jajaprax.de.
authors.forename: Hans
authors.initials: H
authors.lastname: Jaeger
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: michel.janssens@gsk.com.
authors.forename: Michel
authors.initials: M
authors.lastname: Janssens
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: wivine.burny@gsk.com.
authors.forename: Wivine
authors.initials: W
authors.lastname: Burny
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: alix.collard@gsk.com.
authors.forename: Alix
authors.initials: A
authors.lastname: Collard
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: francois.p.roman@gsk.com.
authors.forename: François
authors.initials: F
authors.lastname: Roman
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: edde.loeliger@hotmail.co.uk.
authors.forename: Alfred
authors.initials: A
authors.lastname: Loeliger
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: marguerite.koutsoukos@gsk.com.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: patricia.bourguignon@gsk.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourguignon
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: llavreys@telenet.be.
authors.forename: Ludo
authors.initials: L
authors.lastname: Lavreys
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium. Electronic address: gerald.voss@gsk.com.
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D019562:Viral Load; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D044966:Anti-Retroviral Agents; C508594:IL2 protein, human; D007376:Interleukin-2
keywords: AS01 adjuvant; CD4(+) T-cells; HIV-1 infection; HIV-1 vaccine; recombinant F4 fusion protein