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Dose Optimization of H56:IC31 Vaccine for Tuberculosis-Endemic Populations. A Double-Blind, Placebo-controlled, Dose-Selection Trial.
Suliman, Sara; Luabeya, Angelique Kany Kany; Geldenhuys, Hennie; Tameris, Michele; Hoff, Soren T; Shi, Zhongkai; Tait, Dereck; Kromann, Ingrid; Ruhwald, Morten; Rutkowski, Kathryn Tucker; Shepherd, Barbara; Hokey, David; Ginsberg, Ann M; Hanekom, Willem A; Andersen, Peter; Scriba, Thomas J; Hatherill, Mark.
Afiliação
  • Suliman S; 1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and.
  • Luabeya AKK; 2 Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
  • Geldenhuys H; 1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and.
  • Tameris M; 2 Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
  • Hoff ST; 1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and.
  • Shi Z; 2 Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
  • Tait D; 1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and.
  • Kromann I; 2 Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
  • Ruhwald M; 3 Statens Serum Institut, Copenhagen, Denmark.
  • Rutkowski KT; 4 Aeras, Rockville, Maryland; and.
  • Shepherd B; 5 Aeras, Cape Town, South Africa.
  • Hokey D; 3 Statens Serum Institut, Copenhagen, Denmark.
  • Ginsberg AM; 3 Statens Serum Institut, Copenhagen, Denmark.
  • Hanekom WA; 4 Aeras, Rockville, Maryland; and.
  • Andersen P; 4 Aeras, Rockville, Maryland; and.
  • Scriba TJ; 4 Aeras, Rockville, Maryland; and.
  • Hatherill M; 4 Aeras, Rockville, Maryland; and.
Am J Respir Crit Care Med ; 199(2): 220-231, 2019 01 15.
Article em En | MEDLINE | ID: mdl-30092143
RATIONALE: Global tuberculosis (TB) control requires effective vaccines in TB-endemic countries, where most adults are infected with Mycobacterium tuberculosis (M.tb). OBJECTIVES: We sought to define optimal dose and schedule of H56:IC31, an experimental TB vaccine comprising Ag85B, ESAT-6, and Rv2660c, for M.tb-infected and M.tb-uninfected adults. METHODS: We enrolled 98 healthy, HIV-uninfected, bacillus Calmette-Guérin-vaccinated, South African adults. M.tb infection was defined by QuantiFERON-TB (QFT) assay. QFT-negative participants received two vaccinations of different concentrations of H56 in 500 nmol of IC31 to enable dose selection for further vaccine development. Subsequently, QFT-positive and QFT-negative participants were randomized to receive two or three vaccinations to compare potential schedules. Participants were followed for safety and immunogenicity for 292 days. MEASUREMENTS AND MAIN RESULTS: H56:IC31 showed acceptable reactogenicity profiles irrespective of dose, number of vaccinations, or M.tb infection. No vaccine-related severe or serious adverse events were observed. The three H56 concentrations tested induced equivalent frequencies and functional profiles of antigen-specific CD4 T cells. ESAT-6 was only immunogenic in QFT-negative participants who received three vaccinations. CONCLUSIONS: Two or three H56:IC31 vaccinations at the lowest dose induced durable antigen-specific CD4 T-cell responses with acceptable safety and tolerability profiles in M.tb-infected and M.tb-uninfected adults. Additional studies should validate applicability of vaccine doses and regimens to both QFT-positive and QFT-negative individuals. Clinical trial registered with www.clinicaltrials.gov (NCT01865487).
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose / Vacinas contra a Tuberculose Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose / Vacinas contra a Tuberculose Idioma: En Ano de publicação: 2019 Tipo de documento: Article