title: 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 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.
authors.affiliation: Center for Vaccinology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. Isabel.LerouxRoels@UGent.be
authors.forename: Isabel
authors.initials: I
authors.lastname: Leroux-Roels
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Els
authors.initials: E
authors.lastname: De Kock
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clement
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitié
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006805:Human Experimentation; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D008297:Male; D008875:Middle Aged; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; C539343:Mtb72F-AS02A vaccine; D032581:Tuberculosis Vaccines