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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.

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 ?g antigen), Mtb72F/saline (10 or 40 ?g 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-?g and 40-?g 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-?); CD40L, IL-2, and TNF-?; and CD40L, IL-2, TNF-?, and gamma interferon (IFN-?). Serum IFN-?, but not TNF-?, 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-?g Mtb72F/AS02(A) vaccines show comparable safety and immunogenicity profiles.

SUBMITTER: Leroux-Roels I 

PROVIDER: S-EPMC2976103 | BioStudies | 2010-01-01

REPOSITORIES: biostudies

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