Your browser doesn't support javascript.
loading
Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials.
Norrby, Maria; Vesikari, Timo; Lindqvist, Lars; Maeurer, Markus; Ahmed, Raija; Mahdavifar, Shahnaz; Bennett, Sean; McClain, J Bruce; Shepherd, Barbara M; Li, Daner; Hokey, David A; Kromann, Ingrid; Hoff, Søren T; Andersen, Peter; de Visser, Adriëtte W; Joosten, Simone A; Ottenhoff, Tom H M; Andersson, Jan; Brighenti, Susanna.
Afiliación
  • Norrby M; Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
  • Vesikari T; Vaccine Research Center, University of Tampere, Tampere, Finland.
  • Lindqvist L; Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
  • Maeurer M; TIM, Department of Laboratory Medicine and CAST, Karolinska Institutet, Stockholm, Sweden.
  • Ahmed R; TIM, Department of Laboratory Medicine and CAST, Karolinska Institutet, Stockholm, Sweden.
  • Mahdavifar S; TIM, Department of Laboratory Medicine and CAST, Karolinska Institutet, Stockholm, Sweden.
  • Bennett S; Aeras, Rockville, MD, USA.
  • McClain JB; Aeras, Rockville, MD, USA.
  • Shepherd BM; Aeras, Rockville, MD, USA.
  • Li D; Aeras, Rockville, MD, USA.
  • Hokey DA; Aeras, Rockville, MD, USA.
  • Kromann I; Statens Serum Institut, Copenhagen, Denmark.
  • Hoff ST; Statens Serum Institut, Copenhagen, Denmark.
  • Andersen P; Statens Serum Institut, Copenhagen, Denmark.
  • de Visser AW; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
  • Joosten SA; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
  • Ottenhoff THM; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
  • Andersson J; Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Center for Infectious Medicine (CIM), Karolinska Institutet, Stockholm, Sweden.
  • Brighenti S; Center for Infectious Medicine (CIM), Karolinska Institutet, Stockholm, Sweden. Electronic address: susanna.brighenti@ki.se.
Vaccine ; 35(12): 1652-1661, 2017 03 14.
Article en En | MEDLINE | ID: mdl-28216183
BACKGROUND: Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant. METHODS: BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150µg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4+ T cell responses. RESULTS: H4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4+ T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4+ T cell expansion, IFN-γ production and multifunctional CD4+ Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50µg of H4 in combination with the 500nmol IC31 adjuvant dose. CONCLUSIONS: The novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4+ T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50µg of H4 and 500nmol of IC31. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02066428 and NCT02074956.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Vacunas contra la Tuberculosis Tipo de estudio: Clinical_trials Límite: Adult / Humans País/Región como asunto: Europa Idioma: En Revista: Vaccine Año: 2017 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Vacunas contra la Tuberculosis Tipo de estudio: Clinical_trials Límite: Adult / Humans País/Región como asunto: Europa Idioma: En Revista: Vaccine Año: 2017 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Países Bajos