PMID- 25424924
OWN - NLM
STAT- MEDLINE
DCOM- 20150727
LR  - 20220318
IS  - 2164-554X (Electronic)
IS  - 2164-5515 (Print)
IS  - 2164-5515 (Linking)
VI  - 10
IP  - 8
DP  - 2014
TI  - Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted 
      vaccines: randomized, double-blind study in malaria-naive adults.
PG  - 2211-9
LID - 10.4161/hv.29375 [doi]
AB  - This phase II, randomized, double-blind study evaluated the immunogenicity of 
      RTS,S vaccines containing Adjuvant System AS01 or AS02 as compared with 
      non-adjuvanted RTS,S in healthy, malaria-naive adults (NCT00443131). Thirty-six 
      subjects were randomized (1:1:1) to receive RTS,S/AS01, RTS,S/AS02, or 
      RTS,S/saline at months 0, 1, and 2. Antibody responses to Plasmodium falciparum 
      circumsporozoite (CS) and hepatitis B surface (HBs) antigens were assessed and 
      cell-mediated immune responses evaluated by flow cytometry using intracellular 
      cytokine staining on peripheral blood mononuclear cells. Anti-CS antibody avidity 
      was also characterized. Safety and reactogenicity after each vaccine dose were 
      monitored. One month after the third vaccine dose, RTS,S/AS01 (160.3 EU/mL 
      [95%CI: 114.1-225.4]) and RTS,S/AS02 (77.4 EU/mL (95%CI: 47.3-126.7)) recipients 
      had significantly higher anti-CS antibody geometric mean titers (GMTs) than 
      recipients of RTS,S/saline (12.2 EU/mL (95%CI: 4.8-30.7); P < 0.0001 and P = 
      0.0011, respectively). The anti-CS antibody GMT was significantly higher with 
      RTS,S/AS01 than with RTS,S/AS02 (P = 0.0135). Anti-CS antibody avidity was in the 
      same range in all groups. CS- and HBs-specific CD4(+) T cell responses were 
      greater for both RTS,S/AS groups than for the RTS,S/saline group. Reactogenicity 
      was in general higher for RTS,S/AS compared with RTS,S/saline. Most grade 3 
      solicited adverse events (AEs) were of short duration and grade 3 solicited 
      general AEs were infrequent in the 3 groups. No serious adverse events were 
      reported. In conclusion, in comparison with non-adjuvanted RTS,S, both RTS,S/AS 
      vaccines exhibited better CS-specific immune responses. The anti-CS antibody 
      response was significantly higher with RTS,S/AS01 than with RTS,S/AS02. The 
      adjuvanted vaccines had acceptable safety profiles.
FAU - Leroux-Roels, Geert
AU  - Leroux-Roels G
AD  - a Centre for Vaccinology (CEVAC); Ghent University and Ghent University Hospital; 
      Ghent, Belgium.
FAU - Leroux-Roels, Isabel
AU  - Leroux-Roels I
FAU - Clement, Frederic
AU  - Clement F
FAU - Ofori-Anyinam, Opokua
AU  - Ofori-Anyinam O
FAU - Lievens, Marc
AU  - Lievens M
FAU - Jongert, Erik
AU  - Jongert E
FAU - Moris, Philippe
AU  - Moris P
FAU - Ballou, W Ripley
AU  - Ballou WR
FAU - Cohen, Joe
AU  - Cohen J
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Vaccin Immunother
JT  - Human vaccines & immunotherapeutics
JID - 101572652
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Cytokines)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Protozoan Proteins)
RN  - 0 (RTS,S-AS01 vaccine)
RN  - 0 (RTS,S-AS02A vaccine)
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (circumsporozoite protein, Protozoan)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Protozoan/blood
MH  - Antibody Affinity
MH  - Cytokines/analysis
MH  - Double-Blind Method
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - Flow Cytometry
MH  - Healthy Volunteers
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology
MH  - Malaria Vaccines/administration & dosage/adverse effects/*immunology
MH  - Male
MH  - Plasmodium falciparum/immunology
MH  - Protozoan Proteins/immunology
MH  - Treatment Outcome
MH  - Vaccines, Synthetic/administration & dosage/adverse effects/*immunology
MH  - Young Adult
PMC - PMC4896765
OTO - NOTNLM
OT  - AS01
OT  - AS02
OT  - adjuvant
OT  - cell-mediated immunity
OT  - humoral immunity
OT  - malaria
OT  - vaccine
EDAT- 2014/11/27 06:00
MHDA- 2015/07/28 06:00
PMCR- 2015/06/24
CRDT- 2014/11/27 06:00
PHST- 2014/11/27 06:00 [entrez]
PHST- 2014/11/27 06:00 [pubmed]
PHST- 2015/07/28 06:00 [medline]
PHST- 2015/06/24 00:00 [pmc-release]
AID - 10929375 [pii]
AID - 10.4161/hv.29375 [doi]
PST - ppublish
SO  - Hum Vaccin Immunother. 2014;10(8):2211-9. doi: 10.4161/hv.29375.