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

• Published in: The Journal of infectious diseases 2005-02, Vol.191 (4), p.619-626
• Main Authors: Bejon, Philip, Andrews, Laura, Andersen, Rikke F., Dunachie, Susanna, Webster, Daniel, Walther, Michael, Gilbert, Sarah C., Peto, Tim, Hill, Adrian V. S.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Applied microbiology; Bayes Theorem; Biological and medical sciences; Blood - parasitology; DNA; DNA, Protozoan - analysis; Fundamental and applied biological sciences. Psychology; Human protozoal diseases; Humans; Immunization; Infectious diseases; Liver; Liver - parasitology; Malaria; Malaria - immunology; Malaria - parasitology; Malaria - prevention & control; Malaria vaccine; Malaria Vaccines - administration & dosage; Malaria Vaccines - immunology; Markov Chains; Medical sciences; Microbiology; Models, Biological; Models, Statistical; Nonlinear Dynamics; Parasites; Parasitic diseases; Plasmodium falciparum; Plasmodium falciparum - growth & development; Plasmodium falciparum - immunology; Plasmodium falciparum - isolation & purification; Polymerase Chain Reaction; Protozoal diseases; Regression Analysis; Sporozoites; Sporozoites - growth & development; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Volunteerism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/427243

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]).