Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates
| Autor: | Dan Huang, Andrew A. Lackner, Peter J. Didier, Huiyong Wei, Pyone P. Aye, William R. Jacobs, Richard Frothingham, Vasan K. Sambandamurthy, Tsungda Hsu, Norman L. Letvin, Linyun Shao, Zheng W. Chen, Michelle H. Larsen, Barton F. Haynes, Bing Chen, Karolin Biermann |
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| Rok vydání: | 2009 |
| Předmět: |
Tuberculosis
Carboxy-Lyases Virulence Factors Vaccines Attenuated Severity of Illness Index Article Mycobacterium tuberculosis Interferon-gamma Immune system Bacterial Proteins medicine Animals Tuberculosis Vaccines Lung General Veterinary General Immunology and Microbiology biology Body Weight Public Health Environmental and Occupational Health biology.organism_classification medicine.disease Survival Analysis Virology Vaccination Macaca fascicularis C-Reactive Protein Infectious Diseases Immunization Immunology BCG Vaccine Leukocytes Mononuclear Molecular Medicine Tuberculosis vaccines BCG vaccine Gene Deletion Mycobacterium |
| Zdroj: | Vaccine. 27:4709-4717 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2009.05.050 |
| Popis: | Tuberculosis (TB) remains a global health burden for which safe vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is necessary to demonstrate safety in non-human primates (NHP). In this study, we evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains mc(2)6020 (DeltalysA DeltapanCD) and mc(2)6030 (DeltaRD1 DeltapanCD) in cynomolgus macaques. In murine models, mc(2)6020 is rapidly cleared while mc(2)6030 persists. Both mc(2)6020 and mc(2)6030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc(2)6020-vaccinates were afforded a level of protection intermediate between that elicited by BCG vaccination and no vaccination. BCG vaccinates had reduced tuberculosis-associated pathology and improved clinical scores as compared to saline and mc(2)6030 vaccinates, but survival did not differ among the groups. |
| Databáze: | OpenAIRE |
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