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Defined Tuberculosis Vaccine, Mtb72F/As02a, Evidence of Protection in Cynomolgus Monkeys
Proceedings of the National Academy of Sciences of the United States of America
  • Steven G. Reed
  • Rhea N. Coler
  • Wilfried Dalemans
  • Esterlina V. Tan
  • Eduardo C. DeLa Cruz
  • Randall J. Basaraba
  • Ian M. Orme
  • Yasir A. Skeiky
  • Mark R. Alderson
  • Karen D. Cowgill, University of Washington Tacoma
  • Jean-Paul Prieels
  • Rodolfo M. Abalos
  • Marie-Claude Dubois
  • Joe Cohen
  • Pascal Mettens
  • Yves Lobet
Publication Date
2-17-2009
Document Type
Article
Abstract
The development of a vaccine for tuberculosis requires a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. We evaluated Mtb72F formulated in AS02A in the cynomolgus monkey model. The vaccine was immunogenic and caused no adverse reactions. When monkeys were immunized with bacillus Calmette-Guérin (BCG) and then boosted with Mtb72F in AS02A, protection superior to that afforded by using BCG alone was achieved, as measured by clinical parameters, pathology, and survival. We observed long-term survival and evidence of reversal of disease progression in monkeys immunized with the prime-boost regimen. Antigen-specific responses from protected monkeys receiving BCG and Mtb72F/AS02A had a distinctive cytokine profile characterized by an increased ratio between 3 Th1 cytokines, IFN-gamma, TNF, and IL-2 and an innate cytokine, IL-6. To our knowledge, this is an initial report of a vaccine capable of inducing long-term protection against tuberculosis in a nonhuman primate model, as determined by protection against severe disease and death, and by other clinical and histopathological parameters.
DOI
10.1073/pnas.0712077106
Version
open access
Citation Information
Steven G. Reed, Rhea N. Coler, Wilfried Dalemans, Esterlina V. Tan, et al.. "Defined Tuberculosis Vaccine, Mtb72F/As02a, Evidence of Protection in Cynomolgus Monkeys" Proceedings of the National Academy of Sciences of the United States of America Vol. 106 Iss. 7 (2009) p. 2301 - 2306
Available at: http://works.bepress.com/karen-cowgill/21/