Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys.
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.
Reed
Steven G
SG
Corixa Corporation, Seattle, WA 98104, USA. sreed@idri.org
Coler
Rhea N
RN
Dalemans
Wilfried
W
Dalemans
Wilifred
W
Tan
Esterlina V
EV
DeLa Cruz
Eduardo C
EC
Basaraba
Randall J
RJ
Orme
Ian M
IM
Skeiky
Yasir A W
YA
Alderson
Mark R
MR
Cowgill
Karen D
KD
Prieels
Jean-Paul
JP
Abalos
Rodolfo M
RM
Dubois
Marie-Claude
MC
Cohen
Joe
J
Mettens
Pascal
P
Lobet
Yves
Y
D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D000882:Haplorhini; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008252:Macaca fascicularis; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D015850:Interleukin-6; C539343:Mtb72F-AS02A vaccine; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma