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Evaluation of the Safety and Immunogenicity of Two Antigen Concentrations of the Mtb72F/AS02 A Candidate Tuberculosis Vaccine in Purified Protein Derivative-Negative Adults

2010; American Society for Microbiology; Volume: 17; Issue: 11 Linguagem: Inglês

10.1128/cvi.00133-10

1556-6811

Isabel Leroux‐Roels, Geert Leroux‐Roels, Opokua Ofori‐Anyinam, Philippe Moris, Els De Kock, Frédéric Clement, Marie‐Claude Dubois, Marguerite Koutsoukos, Marie‐Ange Demoitié, Joe Cohen, W. Ripley Ballou,

Pneumonia and Respiratory Infections

ABSTRACT Tuberculosis (TB) remains a major cause of illness and death worldwide, making a new TB vaccine an urgent public health priority. Purified protein derivative (PPD)-negative adults ( n = 50) were equally randomized to receive 3 doses at 1-month intervals (at 0, 1, and 2 months) of one of the following vaccines: Mtb72F/AS02 A (10 or 40 μg antigen), Mtb72F/saline (10 or 40 μg antigen), or AS02 A . Mtb72F/AS02 A recipients received an additional dose 1 year after the first dose to evaluate if the elicited immune response could be boosted. Mtb72F/AS02 A vaccines were locally reactogenic but clinically well tolerated, with transient adverse events (usually lasting between 1 and 4 days) that resolved without sequelae being observed. No vaccine-related serious adverse events were reported. Vaccination with Mtb72F/AS02 A induced a strong Mtb72F-specific humoral response and a robust Mtb72F-specific CD4 + T-cell response, both of which persisted at 9 months after primary immunization and for 1 year after the booster immunization. There was no significant difference between the magnitude of the CD4 + T-cell response induced by the 10-μg and 40-μg Mtb72F/AS02 A vaccines. The Mtb72F-specific CD4 + T cells predominantly expressed CD40L; CD40L and interleukin-2 (IL-2); CD40L and tumor necrosis factor alpha (TNF-α); CD40L, IL-2, and TNF-α; and CD40L, IL-2, TNF-α, and gamma interferon (IFN-γ). Serum IFN-γ, but not TNF-α, was detected 1 day after doses 2 and 3 for the Mtb72F/AS02 A vaccine but did not persist. Vaccine-induced CD8 + T-cell responses were not detected, and no immune responses were elicited with AS02 A alone. In conclusion, Mtb72F/AS02 A is clinically well tolerated and is highly immunogenic in TB-naïve adults. The 10- and 40-μg Mtb72F/AS02 A vaccines show comparable safety and immunogenicity profiles.