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Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys

by Cohen, Joe , Basaraba, Randall J , Cowgill, Karen D , Prieels, Jean-Paul , Tan, Esterlina V , Alderson, Mark R , Coler, Rhea N , DeLa Cruz, Eduardo C , Dubois, Marie-Claude , Orme, Ian M , Lobet, Yves , Skeiky, Yasir A.W , Reed, Steven G , Abalos, Rodolfo M , Mettens, Pascal , Dalemans, Wilifred

in adjuvants / Adjuvants, Immunologic - chemistry / adverse effects / animal models / Animals / Antigens / Bacteria / Biological Sciences / Cynomolgus / Cytokines / Cytokines - metabolism / death / disease course / Disease Progression / Haplorhini / histopathology / Immune System / immunity / Immunization / interferon-gamma / Interferon-gamma - metabolism / interleukin-2 / interleukin-6 / Interleukin-6 - metabolism / Macaca fascicularis / monkeys / Monkeys & apes / Mycobacterium / Mycobacterium tuberculosis - metabolism / Primates / Survival / T-lymphocytes / Time Factors / Treatment Outcome / Tuberculosis / Tuberculosis - microbiology / Tuberculosis - prevention & control / Tuberculosis Vaccines - chemistry / Tuberculosis Vaccines - immunology / tumor necrosis factors / vaccine development / Vaccines

2009

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Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys

2009

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Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys

2009

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Journal Article

Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys

Cohen, Joe,

Basaraba, Randall J,

Cowgill, Karen D,

Prieels, Jean-Paul,

Tan, Esterlina V,

Alderson, Mark R,

Coler, Rhea N,

DeLa Cruz, Eduardo C,

Dubois, Marie-Claude,

Orme, Ian M,

Lobet, Yves,

Skeiky, Yasir A.W,

Reed, Steven G,

Abalos, Rodolfo M,

Mettens, Pascal,

Dalemans, Wilifred

2009

Overview

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-γ, 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.

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Publisher

National Academy of Sciences,National Acad Sciences

Subject

adjuvants

/ Adjuvants, Immunologic - chemistry

/ Animals