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

J Infect Dis. 2005 Feb 15;191(4):619-26. doi: 10.1086/427243. Epub 2005 Jan 7.

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]).

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology
  • Bayes Theorem
  • Blood / parasitology
  • DNA, Protozoan / analysis
  • Humans
  • Liver / parasitology
  • Malaria / immunology*
  • Malaria / parasitology
  • Malaria / prevention & control*
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Markov Chains
  • Models, Biological
  • Models, Statistical
  • Nonlinear Dynamics
  • Plasmodium falciparum / growth & development*
  • Plasmodium falciparum / immunology
  • Plasmodium falciparum / isolation & purification*
  • Polymerase Chain Reaction
  • Regression Analysis
  • Sporozoites / growth & development
  • Vaccination
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Antigens, Protozoan
  • DNA, Protozoan
  • Malaria Vaccines
  • Vaccines, Synthetic