Evaluation of the Safety and Immunogenicity of a Candidate Tuberculosis Vaccine, MVA85A, Delivered by Aerosol to the Lungs of Macaques
| Autor: | Philip Marsh, Arturo Reyes-Sandoval, G. Betts, Ann Williams, Karen E. Gooch, Nick J. Edwards, Sally Sharpe, Laura Sibley, Mike Dennis, Andrew White, Helen McShane, M. W. Carroll |
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| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Microbiology (medical) Tuberculosis Clinical Biochemistry Immunology Immunization Secondary CD8-Positive T-Lymphocytes Vaccines Attenuated complex mixtures chemistry.chemical_compound Immunity Administration Inhalation Vaccines DNA Animals Immunology and Allergy Medicine Intradermal injection Tuberculosis Vaccines Immunity Mucosal Vaccines Antigens Bacterial Vaccines Synthetic business.industry Immunogenicity Vaccination medicine.disease Mycobacterium bovis Virology chemistry Immunization Macaca Vaccinia business Tuberculosis vaccines Bronchoalveolar Lavage Fluid |
| Zdroj: | Clinical and Vaccine Immunology. 20:663-672 |
| ISSN: | 1556-679X 1556-6811 |
| Popis: | Tuberculosis (TB) is a reemerging disease. The only available vaccine,Mycobacterium bovisBCG, is delivered intradermally and confers highly variable efficacy against pulmonary disease. There is an urgent need for improved vaccination strategies. Murine studies suggest that immunizations delivered directly to the respiratory mucosa might be a more effective route of vaccination. This study compared the immunogenicity of a leading candidate tuberculosis (TB) vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in rhesus macaques, delivered either as an aerosol or as an intradermal boost immunization 12 weeks after an intradermal BCG prime vaccine. Aerosol vaccination was well tolerated. MVA85A delivered by aerosol or by intradermal injection induced antigen-specific immune responses in the periphery and the lung, with a trend toward the highest response when the compartment and route of delivery were matched. The ability of poxvirus-vectored vaccines delivered by the systemic route to induce responses in the mucosal immune compartment in macaques is in contrast to the independent compartmentalization of mucosal and systemic immune systems described in mice. Unlike intradermal vaccination, aerosol vaccination did not induce a detectable serum anti-vector antibody response. The delivery of vaccines to the lungs might provide an immunization strategy that limits the induction of systemic anti-vector immunity, which would be extremely useful in the development of improved vaccine strategies. This is the first study to show a recombinant MVA-vectored vaccine to be highly immunogenic when delivered by the aerosol route to nonhuman primates. These results provide important safety and proof-of-concept data for further evaluation of this route of immunization for use in human clinical trials. |
| Databáze: | OpenAIRE |
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