title: 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.
abstract: 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]).
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Rikke F
authors.initials: RF
authors.lastname: Andersen
authors.forename: Susanna
authors.initials: S
authors.lastname: Dunachie
authors.forename: Daniel
authors.initials: D
authors.lastname: Webster
authors.forename: Michael
authors.initials: M
authors.lastname: Walther
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Tim
authors.initials: T
authors.lastname: Peto
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: 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
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic