title: A novel liposomal adjuvant system, CAF01, promotes long-lived Mycobacterium tuberculosis-specific T-cell responses in human.
abstract: Here, we report on a first-in-man trial where the tuberculosis (TB) vaccine Ag85B-ESAT-6 (H1) was adjuvanted with escalating doses of a novel liposome adjuvant CAF01. On their own, protein antigens cannot sufficiently induce immune responses in humans, and require the addition of an adjuvant system to ensure appropriate delivery and concomitant immune activation. To date no approved adjuvants are available for induction of cellular immunity, which seems essential for a number of vaccines, including vaccines against TB. We vaccinated four groups of human volunteers: a non-adjuvanted H1 group, followed by three groups with escalating doses of CAF01-adjuvanted H1 vaccine. All subjects were vaccinated at 0 and 8 weeks and followed up for 150 weeks. Vaccination did not cause local or systemic adverse effects besides transient soreness at the injection site. Two vaccinations elicited strong antigen-specific T-cell responses which persisted after 150 weeks follow-up, indicating the induction of a long-lasting memory response in the vaccine recipients. These results show that CAF01 is a safe and tolerable, Th1-inducing adjuvant for human TB vaccination trials and for vaccination studies in general where cellular immunity is required.
authors.affiliation: Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands. Electronic address: j.t.van_dissel@lumc.nl.
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.affiliation: Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Joosten
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Artillerivej 5, Copenhagen 2300s, Denmark.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Hoff
authors.affiliation: Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands.
authors.forename: Darius
authors.initials: D
authors.lastname: Soonawala
authors.affiliation: Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands.
authors.forename: Corine
authors.initials: C
authors.lastname: Prins
authors.affiliation: Aeras, Rockville, MD, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hokey
authors.affiliation: Aeras, Rockville, MD, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: O'Dee
authors.affiliation: Aeras, Rockville, MD, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Graves
authors.affiliation: Statens Serum Institut, Department of Vaccine Development, Artillerivej 5, Copenhagen 2300s, Denmark.
authors.forename: Birgit
authors.initials: B
authors.lastname: Thierry-Carstensen
authors.affiliation: Statens Serum Institut, Department of Vaccine Development, Artillerivej 5, Copenhagen 2300s, Denmark.
authors.forename: Lars V
authors.initials: LV
authors.lastname: Andreasen
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Artillerivej 5, Copenhagen 2300s, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.affiliation: Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands.
authors.forename: Adriëtte W
authors.initials: AW
authors.lastname: de Visser
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Artillerivej 5, Copenhagen 2300s, Denmark.
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.affiliation: Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands.
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Statens Serum Institut, Department of Vaccine Development, Artillerivej 5, Copenhagen 2300s, Denmark.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kromann
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Artillerivej 5, Copenhagen 2300s, Denmark. Electronic address: PA@ssi.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007156:Immunologic Memory; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D013601:T-Lymphocytes / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; C557979:Ag85B-ESAT-6 fusion antigen; D008081:Liposomes; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines
keywords: Adjuvant; Clinical trial; Immunogenicity; Tuberculosis; Vaccine