PMID- 21862998
OWN - NLM
STAT- MEDLINE
DCOM- 20120322
LR  - 20220129
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 19
IP  - 12
DP  - 2011 Dec
TI  - Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen 
      MSP1 in ChAd63 and MVA vaccine vectors.
PG  - 2269-76
LID - 10.1038/mt.2011.176 [doi]
AB  - Efficacy trials of antibody-inducing protein-in-adjuvant vaccines targeting the 
      blood-stage Plasmodium falciparum malaria parasite have so far shown 
      disappointing results. The induction of cell-mediated responses in conjunction 
      with antibody responses is thought to be one alternative strategy that could 
      achieve protective efficacy in humans. Here, we prepared chimpanzee adenovirus 63 
      (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient vectors 
      encoding the well-studied P. falciparum blood-stage malaria antigen merozoite 
      surface protein 1 (MSP1). A phase Ia clinical trial was conducted in healthy 
      adults of a ChAd63-MVA MSP1 heterologous prime-boost immunization regime. The 
      vaccine was safe and generally well tolerated. Fewer systemic adverse events 
      (AEs) were observed following ChAd63 MSP1 than MVA MSP1 administration. 
      Exceptionally strong T-cell responses were induced, and these displayed a mixed 
      of CD4(+) and CD8(+) phenotype. Substantial MSP1-specific serum immunoglobulin G 
      (IgG) antibody responses were also induced, which were capable of recognizing 
      native parasite antigen, but these did not reach titers sufficient to neutralize 
      P. falciparum parasites in vitro. This viral vectored vaccine regime is thus a 
      leading approach for the induction of strong cellular and humoral immunogenicity 
      against difficult disease targets in humans. Further studies are required to 
      assess whether this strategy can achieve protective efficacy against blood-stage 
      malaria infection.
FAU - Sheehy, Susanne H
AU  - Sheehy SH
AD  - Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, 
      University of Oxford, Churchill Hospital, Oxford, UK. susanne.sheehy@ndm.ox.ac.uk
FAU - Duncan, Christopher J A
AU  - Duncan CJ
FAU - Elias, Sean C
AU  - Elias SC
FAU - Collins, Katharine A
AU  - Collins KA
FAU - Ewer, Katie J
AU  - Ewer KJ
FAU - Spencer, Alexandra J
AU  - Spencer AJ
FAU - Williams, Andrew R
AU  - Williams AR
FAU - Halstead, Fenella D
AU  - Halstead FD
FAU - Moretz, Samuel E
AU  - Moretz SE
FAU - Miura, Kazutoyo
AU  - Miura K
FAU - Epp, Christian
AU  - Epp C
FAU - Dicks, Matthew D J
AU  - Dicks MD
FAU - Poulton, Ian D
AU  - Poulton ID
FAU - Lawrie, Alison M
AU  - Lawrie AM
FAU - Berrie, Eleanor
AU  - Berrie E
FAU - Moyle, Sarah
AU  - Moyle S
FAU - Long, Carole A
AU  - Long CA
FAU - Colloca, Stefano
AU  - Colloca S
FAU - Cortese, Riccardo
AU  - Cortese R
FAU - Gilbert, Sarah C
AU  - Gilbert SC
FAU - Nicosia, Alfredo
AU  - Nicosia A
FAU - Hill, Adrian V S
AU  - Hill AV
FAU - Draper, Simon J
AU  - Draper SJ
LA  - eng
GR  - G1000527(95710)/MRC_/Medical Research Council/United Kingdom
GR  - G0700735/MRC_/Medical Research Council/United Kingdom
GR  - 095540/Wellcome Trust/United Kingdom
GR  - 084113/Z/07/Z/WT_/Wellcome Trust/United Kingdom
GR  - 45488/Z/05/WT_/Wellcome Trust/United Kingdom
GR  - G1000527/MRC_/Medical Research Council/United Kingdom
GR  - 090532/Wellcome Trust/United Kingdom
GR  - G1000527/WT_/Wellcome Trust/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110823
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Merozoite Surface Protein 1)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Adjuvants, Immunologic
MH  - Adult
MH  - Animals
MH  - Antibodies, Protozoan/immunology
MH  - Blotting, Western
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Genetic Vectors/*therapeutic use
MH  - Humans
MH  - Immunity, Cellular
MH  - Immunoglobulin G/immunology
MH  - Immunologic Memory
MH  - Macaca mulatta
MH  - Malaria, Falciparum/blood/*immunology/*therapy
MH  - Male
MH  - Merozoite Surface Protein 1/blood/genetics/*immunology
MH  - Mice
MH  - Plasmodium falciparum/genetics/immunology
MH  - Vaccination
MH  - Vaccinia virus/*genetics
MH  - Young Adult
PMC - PMC3242658
EDAT- 2011/08/25 06:00
MHDA- 2012/03/23 06:00
PMCR- 2012/12/01
CRDT- 2011/08/25 06:00
PHST- 2011/08/25 06:00 [entrez]
PHST- 2011/08/25 06:00 [pubmed]
PHST- 2012/03/23 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - S1525-0016(16)32712-5 [pii]
AID - 10.1038/mt.2011.176 [doi]
PST - ppublish
SO  - Mol Ther. 2011 Dec;19(12):2269-76. doi: 10.1038/mt.2011.176. Epub 2011 Aug 23.