Safety, immunogenicity, and efficacy of prime-boost immunization with recombinant poxvirus FP9 and modified vaccinia virus Ankara encoding the full-length Plasmodium falciparum circumsporozoite protein.
Heterologous prime-boost immunization with DNA and various recombinant poxviruses encoding malaria antigens is capable of inducing strong cell-mediated immune responses and partial protection in human sporozoite challenges. Here we report a series of trials assessing recombinant fowlpox virus and modified vaccinia virus Ankara encoding the Plasmodium falciparum circumsporozoite protein in various prime-boost combinations, doses, and application routes. For the first time, these vaccines were administered intramuscularly and at doses of up to 5 x 10(8) PFU. Vaccines containing this antigen proved safe and induced modest immune responses but showed no evidence of efficacy in a sporozoite challenge.
Walther
Michael
M
Centre for Clinical Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom. mwalther@mrc.gm
Thompson
Fiona M
FM
Dunachie
Susanna
S
Keating
Sheila
S
Todryk
Stephen
S
Berthoud
Tamara
T
Andrews
Laura
L
Andersen
Rikke F
RF
Moore
Anne
A
Gilbert
Sarah C
SC
Poulton
Ian
I
Dubovsky
Filip
F
Tierney
Eveline
E
Correa
Simon
S
Huntcooke
Angela
A
Butcher
Geoffrey
G
Williams
Jack
J
Sinden
Robert E
RE
Hill
Adrian V S
AV
D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002986:Clinical Trials as Topic; D017261:Glycosylphosphatidylinositols / Q000502:physiology; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D018512:Parasitemia / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D011212:Poxviridae / Q000235:genetics; D015800:Protozoan Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D000913:Antibodies, Protozoan; D017261:Glycosylphosphatidylinositols; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; C081751:plasmanylinositol glycan; D007371:Interferon-gamma