期刊
VACCINE
卷 29, 期 29-30, 页码 4839-4847出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.04.066
关键词
Tuberculosis; Vaccine; Auxotroph; SIV; Rhesus macaque; Guinea pig
资金
- Aeras Global TB Vaccine Foundation
- National Institute of Health [AI023545]
We have previously described the development of a live, fully attenuated Mycobacterium tuberculosis (Mtb) vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. In the present work, those studies have been extended to include testing for protective efficacy in a long-term guinea pig survival model and safety testing in the highly tuberculosis susceptible Rhesus macaque. To model the safety of the Delta leuD Delta panCD strain in HIV-infected human populations, a Simian immunodeficiency virus (SIV)-infected Rhesus macaque group was included. Immunization with the non-replicating Delta leuD Delta panCD conferred long-term protection against challenge with virulent M. tuberculosis equivalent to that afforded by BCG as measured by guinea pig survival. In safety studies, clinical, hematological and bacteriological monitoring of both SIV-positive and Sly-negative Rhesus macaques immunized with Delta leuD Delta panCD, revealed no vaccine-associated adverse effects. The results support the further development of the Delta leuD Delta panCD strain as a viable tuberculosis (TB) vaccine candidate. (C) 2011 Elsevier Ltd. All rights reserved.
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