Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara.
Malaria is a major global health problem for which an effective vaccine is required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage malaria antigens have been shown to be powerfully immunogenic for T cells and capable of inducing partial protection against experimental malaria challenge in humans, manifested as a delay in time to patent parasitemia. Here, we report that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months. Protection at 20 months was associated with persisting memory but not effector T cell responses. The protective efficacy of various immunization regimes correlated with the magnitude of induced immune responses, supporting the strategy of maximizing durable T cell immunogenicity to develop more effective liver-stage vaccines against Plasmodium falciparum malaria.
Webster
Daniel P
DP
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK.
Dunachie
Susanna
S
Vuola
Jenni M
JM
Berthoud
Tamara
T
Keating
Sheila
S
Laidlaw
Stephen M
SM
McConkey
Samuel J
SJ
Poulton
Ian
I
Andrews
Laura
L
Andersen
Rikke F
RF
Bejon
Philip
P
Butcher
Geoff
G
Sinden
Robert
R
Skinner
Michael A
MA
Gilbert
Sarah C
SC
Hill
Adrian V S
AV
D000328:Adult; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005587:Fowlpox virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma