Evaluation of the safety and immunogenicity of two antigen concentrations of the Mtb72F/AS02(A) candidate tuberculosis vaccine in purified protein derivative-negative adults

• Published in: Clinical and vaccine immunology 2010-11, Vol.17 (11), p.1763-1771
• Main Authors: Leroux-Roels, Isabel, Leroux-Roels, Geert, Ofori-Anyinam, Opokua, Moris, Philippe, De Kock, Els, Clement, Frédéric, Dubois, Marie-Claude, Koutsoukos, Marguerite, Demoitié, Marie-Ange, Cohen, Joe, Ballou, W Ripley
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies, Bacterial - blood; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cytokines - secretion; Female; Human Experimentation; Humans; Immunization, Secondary - methods; Male; Middle Aged; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - adverse effects; Tuberculosis Vaccines - immunology; Vaccination - methods; Young Adult
• ISSN: 1556-6811; 1556-679X
• DOI: 10.1128/CVI.00133-10

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.