Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants.
J Infect Dis
; 203(12): 1832-43, 2011 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-21606542
ABSTRACT
BACKGROUND:
BCG, the only licensed tuberculosis vaccine, affords poor protection against lung tuberculosis in infants and children. A new tuberculosis vaccine, which may enhance the BCG-induced immune response, is urgently needed. We assessed the safety of and characterized the T cell response induced by 3 doses of the candidate vaccine, MVA85A, in BCG-vaccinated infants from a setting where tuberculosis is endemic.METHODS:
Infants aged 5-12 months were vaccinated intradermally with either 2.5 × 10(7), 5 × 10(7), or 10 × 10(7) plaque-forming units of MVA85A, or placebo. Adverse events were documented, and T-cell responses were assessed by interferon γ (IFN-γ) enzyme-linked immunospot assay and intracellular cytokine staining.RESULTS:
The 3 MVA85A doses were well tolerated, and no vaccine-related serious adverse events were recorded. MVA85A induced potent, durable T-cell responses, which exceeded prevaccination responses up to 168 d after vaccination. No dose-related differences in response magnitude were observed. Multiple CD4 T cell subsets were induced; polyfunctional CD4 T cells co-expressing T-helper cell 1 cytokines with or without granulocyte-macrophage colony-stimulating factor predominated. IFN-γ-expressing CD8 T cells, which peaked later than CD4 T cells, were also detectable.CONCLUSIONS:
MVA85A was safe and induced robust, polyfunctional, durable CD4 and CD8 T-cell responses in infants. These data support efficacy evaluation of MVA85A to prevent tuberculosis in infancy. Clinical Trials Registration. NCT00679159.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Linfócitos T CD4-Positivos
/
Vacinas contra a Tuberculose
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Mycobacterium tuberculosis
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Female
/
Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article