Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans.
In animals, effective immune responses against malignancies and against several infectious pathogens, including malaria, are mediated by T cells. Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally, followed by intradermal recombinant modified vaccinia virus Ankara (MVA), induces high frequencies of interferon (IFN)-gamma-secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related adhesion protein (TRAP). These responses are five- to tenfold higher than the T-cell responses induced by the DNA vaccine or recombinant MVA vaccine alone, and produce partial protection manifest as delayed parasitemia after sporozoite challenge with a different strain of Plasmodium falciparum. Such heterologous prime-boost immunization approaches may provide a basis for preventative and therapeutic vaccination in humans.
McConkey
Samuel J
SJ
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Reece
William H H
WH
Moorthy
Vasee S
VS
Webster
Daniel
D
Dunachie
Susanna
S
Butcher
Geoff
G
Vuola
Jenni M
JM
Blanchard
Tom J
TJ
Gothard
Philip
P
Watkins
Kate
K
Hannan
Carolyn M
CM
Everaere
Simone
S
Brown
Karen
K
Kester
Kent E
KE
Cummings
James
J
Williams
Jackie
J
Heppner
D Gray
DG
Pathan
Ansar
A
Flanagan
Katie
K
Arulanantham
Nirmalan
N
Roberts
Mark T M
MT
Roy
Michael
M
Smith
Geoffrey L
GL
Schneider
Joerg
J
Peto
Tim
T
Sinden
Robert E
RE
Gilbert
Sarah C
SC
Hill
Adrian V S
AV
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000628:therapy; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010957:Plasmids; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma