Safety of recombinant fowlpox strain FP9 and modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-immune volunteers.
The ability to generate potent antigen-specific T cell responses by vaccination has been a major hurdle in vaccinology. Vaccinia virus and avipox viruses have been shown to be capable of expressing antigens in mammalian cells and can induce a protective immune response against several mammalian pathogens. We report on two such vaccine constructs, modified vaccinia virus Ankara and FP9 (an attenuated fowlpox virus) both expressing the pre-erythrocytic malaria antigen thrombospondin-related adhesion protein and a string of CD8+ epitopes (ME-TRAP). In prime-boost combinations in a mouse model MVA and FP9 are highly immunogenic and induce substantial protective efficacy. A series of human clinical trials using the recombinant MVA and FP9 malaria vaccines encoding ME-TRAP, both independently and in prime-boost combinations with or without the DNA vaccine DNA ME-TRAP, has shown them to be both immunogenic for CD8+ T cells and capable of inducing protective efficacy. We report here a detailed analysis of the safety profiles of these viral vectors and show that anti-vector antibody responses induced by the vectors are generally low to moderate. We conclude that these vectors are safe and show acceptable side effect profiles for prophylactic vaccination.
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK.
D P
DP
Webster
S
S
Dunachie
S
S
McConkey
I
I
Poulton
A C
AC
Moore
M
M
Walther
S M
SM
Laidlaw
T
T
Peto
M A
MA
Skinner
S C
SC
Gilbert
A V S
AV
Hill
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D004890:Erythema; D005076:Exanthema; D005260:Female; D005586:Fowlpox / Q000235:genetics* / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; C069428:thrombospondin-related adhesive protein, protozoan