title: The candidate tuberculosis vaccine Mtb72F/AS02A: Tolerability and immunogenicity in humans.
abstract: Tuberculosis (TB) remains uncontrolled in many parts of the world and the development of an effective vaccine against TB represents a high priority unmet medical need. Healthy PPD (tuberculin purified protein derivative)-negative adult volunteers, aged 18-40 years received three doses of the candidate Mtb72F/AS02A vaccine according to a 0-1-2 months schedule in an open-label Phase I study (NCT00730795). Solicited, unsolicited and serious adverse events (AEs), hematological and biochemical laboratory parameters were assessed. Mtb72F-specific humoral responses were assessed by ELISA and cell-mediated immune (CMI) responses by intracellular cytokine staining (ICS) and short-term ELISPOT assays. CMI responses to the component peptides (Mtb39a and the Mtb32a C- and N-terminal antigen domains, Mtb32C and Mtb32N) were also assessed by ICS. The Mtb72F/AS02A vaccine appeared to be mainly locally reactogenic but this was considered acceptable, since these AEs were usually transient and resolved within 1-2 days. Most AEs reported were mild in intensity, no serious AEs occurred, no medically significant biochemical or hematological abnormalities related to vaccination were measured and all AEs resolved without sequelae. The vaccine induced statistically significant changes in humoral and CMI response measures. The Mtb72F antigen induced good production of IL-2 and IFNgamma in the ELISPOT assay and CD4(+) T cells expressing at least two activation markers (mainly CD40-L and IL-2) were observed with ICS. A similar CMI profile was observed with Mtb39a and Mtb32N. The induced CMI responses persisted for at least 6 months post-vaccination. All subjects were seropositive for anti-Mtb72F antibodies one month post-dose 2 and 6 months post-dose 3. This first trial in humans found Mtb72F/AS02A to have an acceptable tolerability, to be immunogenic in healthy adults and warrants further development of the vaccine.
authors: GlaxoSmithKline Biologicals, Rixensart, Belgium.
authors: Kenneth
authors: K
authors: Von Eschen
authors: Royce
authors: R
authors: Morrison
authors: Madeleine
authors: M
authors: Braun
authors: Opokua
authors: O
authors: Ofori-Anyinam
authors: Els
authors: E
authors: De Kock
authors: Priya
authors: P
authors: Pavithran
authors: Marguerite
authors: M
authors: Koutsoukos
authors: Philippe
authors: P
authors: Moris
authors: Daniel
authors: D
authors: Cain
authors: Marie-Claude
authors: MC
authors: Dubois
authors: Joe
authors: J
authors: Cohen
authors: W Ripley
authors: WR
authors: Ballou
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D019013:CD40 Antigens / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006805:Human Experimentation; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012871:Skin Diseases / Q000139:chemically induced; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D019013:CD40 Antigens; D016207:Cytokines; C539343:Mtb72F-AS02A vaccine; D032581:Tuberculosis Vaccines