PMID- 19587528
OWN - NLM
STAT- MEDLINE
DCOM- 20090928
LR  - 20190516
IS  - 1554-8619 (Electronic)
IS  - 1554-8600 (Linking)
VI  - 5
IP  - 7
DP  - 2009 Jul
TI  - The candidate tuberculosis vaccine Mtb72F/AS02A: Tolerability and immunogenicity 
      in humans.
PG  - 475-82
AB  - 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.
FAU - Von Eschen, Kenneth
AU  - Von Eschen K
AD  - GlaxoSmithKline Biologicals, Rixensart, Belgium.
FAU - Morrison, Royce
AU  - Morrison R
FAU - Braun, Madeleine
AU  - Braun M
FAU - Ofori-Anyinam, Opokua
AU  - Ofori-Anyinam O
FAU - De Kock, Els
AU  - De Kock E
FAU - Pavithran, Priya
AU  - Pavithran P
FAU - Koutsoukos, Marguerite
AU  - Koutsoukos M
FAU - Moris, Philippe
AU  - Moris P
FAU - Cain, Daniel
AU  - Cain D
FAU - Dubois, Marie-Claude
AU  - Dubois MC
FAU - Cohen, Joe
AU  - Cohen J
FAU - Ballou, W Ripley
AU  - Ballou WR
LA  - eng
SI  - ClinicalTrials.gov/NCT00730795
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090727
PL  - United States
TA  - Hum Vaccin
JT  - Human vaccines
JID - 101265291
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (CD40 Antigens)
RN  - 0 (Cytokines)
RN  - 0 (Mtb72F-AS02A vaccine)
RN  - 0 (Tuberculosis Vaccines)
SB  - IM
MH  - Adult
MH  - Antibodies, Bacterial/blood
MH  - CD4-Positive T-Lymphocytes/chemistry/immunology
MH  - CD40 Antigens/analysis
MH  - Cytokines/biosynthesis/metabolism
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Female
MH  - Human Experimentation
MH  - Humans
MH  - Immunization, Secondary/methods
MH  - Leukocytes, Mononuclear/immunology
MH  - Male
MH  - Middle Aged
MH  - Skin Diseases/chemically induced
MH  - Tuberculosis Vaccines/administration & dosage/*adverse effects/*immunology
MH  - Young Adult
EDAT- 2009/07/10 09:00
MHDA- 2009/09/29 06:00
CRDT- 2009/07/10 09:00
PHST- 2009/07/10 09:00 [entrez]
PHST- 2009/07/10 09:00 [pubmed]
PHST- 2009/09/29 06:00 [medline]
AID - 8570 [pii]
AID - 10.4161/hv.8570 [doi]
PST - ppublish
SO  - Hum Vaccin. 2009 Jul;5(7):475-82. doi: 10.4161/hv.8570. Epub 2009 Jul 27.