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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Extended safety and efficacy studies of a live attenuated double leucine and pantothenate auxotroph of Mycobacterium tuberculosis as a vaccine candidate
Vaccine, Volume 29, No. 29-30, Year 2011
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Description
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 ΔleuD ΔpanCD strain in HIVinfected human populations, a Simian immunodeficiency virus (SIV)-infected Rhesus macaque group was included. Immunization with the non-replicating ΔleuD ΔpanCD 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 SIV-negative Rhesus macaques immunized with ΔleuD ΔpanCD, revealed no vaccine-associated adverse effects. The results support the further development of the ΔleuD ΔpanCD strain as a viable tuberculosis (TB) vaccine candidate. © 2011 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Sampson, Samantha Leigh
United States, Boston
Harvard T.h. Chan School of Public Health
United Kingdom, London
Imperial College London
Mansfield, Keith G.
United States, Southborough
New England Regional Primate Research Center
Carville, Angela A.L.
United States, Southborough
New England Regional Primate Research Center
Magee, D. Mitchell
United States, San Antonio
University of Texas Health Science Center at San Antonio
United States, Tempe
Arizona State University
Howerth, Elizabeth Wynne
United States, Athens
University of Georgia
Bloom, Barry R.
United States, Boston
Harvard T.h. Chan School of Public Health
Hondalus, Mary K.
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Athens
University of Georgia
Statistics
Citations: 31
Authors: 7
Affiliations: 6
Identifiers
Doi:
10.1016/j.vaccine.2011.04.066
ISSN:
0264410X
Research Areas
Infectious Diseases
Maternal And Child Health
Study Locations
Guinea