Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites.
We calculated the number and growth rate of Plasmodium falciparum parasites emerging in recipients of candidate preerythrocytic malaria vaccines and unvaccinated control subjects undergoing mosquito-bite challenge. This was done to measure vaccine efficacy and to distinguish the effects on blood-stage multiplication from those on liver-stage parasites. Real-time polymerase chain reaction measurements of parasite densities were analyzed by nonlinear regression and mixed-effects models. Substantial reductions in numbers of liver parasites resulted from the use of 2 immunization regimens: FP9 boosted by modified virus Ankara (MVA) encoding the malaria epitope-thrombospondin-related adhesion protein insert (92% reduction) and RTS,S/AS02 used in heterologous prime-boost immunization regimens, with MVA encoding the circumsporozoite protein (97% reduction). Forty-eight-hour growth rates in blood from control subjects were not different from those in blood from any vaccination group (mean, 14.4-fold [95% confidence interval, 11-19-fold]).
Bejon
Philip
P
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom.
Andrews
Laura
L
Andersen
Rikke F
RF
Dunachie
Susanna
S
Webster
Daniel
D
Walther
Michael
M
Gilbert
Sarah C
SC
Peto
Tim
T
Hill
Adrian V S
AV
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D001499:Bayes Theorem; D001769:Blood / Q000469:parasitology; D016054:DNA, Protozoan / Q000032:analysis; D006801:Humans; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008390:Markov Chains; D008954:Models, Biological; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D012044:Regression Analysis; D034101:Sporozoites / Q000254:growth & development; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic