Safety and Immunogenicity of a New Tuberculosis Vaccine, MVA85A, in Mycobacterium tuberculosis–infected Individuals
| Autor: | Adrian V. S. Hill, Robert J. O. Davies, Helen McShane, Natalie E. R. Beveridge, Nicola Alder, Angela M. Minassian, Geoffrey Pasvol, Fergus V. Gleeson, Ansar A. Pathan, Johan Van Wijgerden, Clare R. Sander, Ian D. Poulton |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine medicine.medical_specialty Modified vaccinia Ankara Tuberculosis Koch Critical Care and Intensive Care Medicine Mycobacterium tuberculosis Young Adult Tuberculosis diagnosis Internal medicine Intensive care medicine Humans Tuberculosis Vaccines E. Tuberculosis Latent TB Vaccines Synthetic biology Tuberculin Test business.industry Immunogenicity Middle Aged bacterial infections and mycoses medicine.disease biology.organism_classification Vaccination Immunology Female Tuberculosis vaccines business Vaccine Human |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 179:724-733 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.200809-1486oc |
| Popis: | Copyright © 2009 by the American Thoracic Society. Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas. Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|