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Safety and immunogenicity evaluation of recombinant BCG vaccine against respiratory syncytial virus in a randomized, double-blind, placebo-controlled phase I clinical trial.
Abarca, Katia; Rey-Jurado, Emma; Muñoz-Durango, Natalia; Vázquez, Yaneisi; Soto, Jorge A; Gálvez, Nicolás M S; Valdés-Ferrada, Javier; Iturriaga, Carolina; Urzúa, Marcela; Borzutzky, Arturo; Cerda, Jaime; Villarroel, Luis; Madrid, Victoria; González, Pablo A; González-Aramundiz, José V; Bueno, Susan M; Kalergis, Alexis M.
Afiliación
  • Abarca K; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • Rey-Jurado E; Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, División de Pediatría, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Muñoz-Durango N; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • Vázquez Y; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Soto JA; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • Gálvez NMS; Departamento de Endocrinología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Valdés-Ferrada J; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Iturriaga C; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • Urzúa M; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Borzutzky A; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • Cerda J; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Villarroel L; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • Madrid V; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • González PA; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • González-Aramundiz JV; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Bueno SM; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins No. 340, Santiago, Chile.
  • Kalergis AM; Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, División de Pediatría, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
EClinicalMedicine ; 27: 100517, 2020 Oct.
Article en En | MEDLINE | ID: mdl-33073219
BACKGROUND: Respiratory syncytial virus (RSV) is responsible for most respiratory tract infections and hospitalizations in infants and represents a significant economic burden for public health. The development of a safe, effective, and affordable vaccine is a priority for the WHO. METHODS: We conducted a double-blinded, escalating-dose phase 1 clinical trial in healthy males aged 18-50 years to evaluate safety, tolerability, and immunogenicity of a recombinant Mycobacterium bovis BCG vaccine expressing the nucleoprotein of RSV (rBCG-N-hRSV). Once inclusion criteria were met, volunteers were enrolled in three cohorts in an open and successive design. Each cohort included six volunteers vaccinated with 5 × 103, 5 × 104, or 1 × 105 CFU, as well as two volunteers vaccinated with the full dose of the standard BCG vaccine. This clinical trial (clinicaltrials.gov NCT03213405) was conducted in Santiago, Chile. FINDINGS: The rBCG-N-RSV vaccine was safe, well-tolerated, and no serious adverse events related to the vaccine were recorded. Serum IgG-antibodies directed against Mycobacterium and the N-protein of RSV increased after vaccination, which were capable of neutralizing RSV in vitro. Additionally, all volunteers displayed increased cellular response consisting of IFN-γ and IL-2 production against PPD and the N-protein, starting at day 14 and 30 post-vaccination respectively. INTERPRETATION: The rBCG-N-hRSV vaccine had a good safety profile and induced specific cellular and humoral responses. FUNDING: This work was supported by Millennium Institute on Immunology and Immunotherapy from Chile (P09/016), FONDECYT 1190830, and FONDEF D11E1098.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials Idioma: En Revista: EClinicalMedicine Año: 2020 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials Idioma: En Revista: EClinicalMedicine Año: 2020 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Reino Unido