A prime-boost immunisation regimen using DNA followed by recombinant modified vaccinia virus Ankara induces strong cellular immune responses against the Plasmodium falciparum TRAP antigen in chimpanzees.
Two chimpanzees were vaccinated intramuscularly against malaria using plasmid DNA expressing the pre-erythrocytic antigens thrombospondin related adhesion protein (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasmodium falciparum together with GM-CSF protein. A recombinant modified vaccinia virus Ankara (MVA) expressing PfTRAP was injected intramuscularly 6 weeks later to boost the immune response. This sequence of antigen delivery induced a specific and long-lasting T cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA. Antibody responses were detected after four DNA injections, and were boosted by injection of recombinant MVA expressing PfTRAP. Interferon-gamma secreting antigen-specific T cells were detected in both animals, but only after boosting with recombinant MVA. By screening a panel of PfTRAP-derived peptides, an epitope was identified that was recognized by cytotoxic T lymphocytes in one of the chimpanzees studied. T cells specific for this epitope were present in PBMCs and liver-infiltrating lymphocytes at a frequency of between 1 in 200 and 1 in 500. The high immunogenicity of this prime-boost regimen in chimpanzees supports further assessment of this delivery strategy for the induction of protection against P. falciparum malaria in humans.
Schneider
J
J
Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DU, Oxford, UK. joerg@oxxonpharmaccines.com
Langermans
J A
JA
Gilbert
S C
SC
Blanchard
T J
TJ
Twigg
S
S
Naitza
S
S
Hannan
C M
CM
Aidoo
M
M
Crisanti
A
A
Robson
K J
KJ
Smith
G L
GL
Hill
A V
AV
Thomas
A W
AW
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D016054:DNA, Protozoan / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005347:Fibroblasts / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007963:Leukocytes, Mononuclear / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D002679:Pan troglodytes; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C067302:liver stage-specific antigen, Plasmodium; C069428:thrombospondin-related adhesive protein, protozoan; D016178:Granulocyte-Macrophage Colony-Stimulating Factor