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.
Webster
D P
DP
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK.
Dunachie
S
S
McConkey
S
S
Poulton
I
I
Moore
A C
AC
Walther
M
M
Laidlaw
S M
SM
Peto
T
T
Skinner
M A
MA
Gilbert
S C
SC
Hill
A V S
AV
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