Controlled Human Blood Stage Malaria Infection: Current Status and Potential Applications

Duncan, Christopher; Draper, Simon J.

doi:10.4269/ajtmh.2012.11-0504

Cited by 46 publications

(42 citation statements)

References 20 publications

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“…This is an important measure of the reproducibility of the model. The use of the highly sensitive qPCR to monitor parasitemia pretreatment as well as the clearance post antimalarial treatment, not only ensures subject safety, but also allows accurate calculation of the parasite growth rate and PMR [33]. Interestingly, there was not a substantial difference in the parasite growth rate and PMR between cohorts, including cohorts conducted in the P .…”

Section: Discussionmentioning

confidence: 99%

Safety and Reproducibility of a Clinical Trial System Using Induced Blood Stage Plasmodium vivax Infection and Its Potential as a Model to Evaluate Malaria Transmission

et al. 2016

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BackgroundInterventions to interrupt transmission of malaria from humans to mosquitoes represent an appealing approach to assist malaria elimination. A limitation has been the lack of systems to test the efficacy of such interventions before proceeding to efficacy trials in the field. We have previously demonstrated the feasibility of induced blood stage malaria (IBSM) infection with Plasmodium vivax. In this study, we report further validation of the IBSM model, and its evaluation for assessment of transmission of P. vivax to Anopheles stephensi mosquitoes.MethodsSix healthy subjects (three cohorts, n = 2 per cohort) were infected with P. vivax by inoculation with parasitized erythrocytes. Parasite growth was monitored by quantitative PCR, and gametocytemia by quantitative reverse transcriptase PCR (qRT-PCR) for the mRNA pvs25. Parasite multiplication rate (PMR) and size of inoculum were calculated by linear regression. Mosquito transmission studies were undertaken by direct and membrane feeding assays over 3 days prior to commencement of antimalarial treatment, and midguts of blood fed mosquitoes dissected and checked for presence of oocysts after 7–9 days.ResultsThe clinical course and parasitemia were consistent across cohorts, with all subjects developing mild to moderate symptoms of malaria. No serious adverse events were reported. Asymptomatic elevated liver function tests were detected in four of six subjects; these resolved without treatment. Direct feeding of mosquitoes was well tolerated. The estimated PMR was 9.9 fold per cycle. Low prevalence of mosquito infection was observed (1.8%; n = 32/1801) from both direct (4.5%; n = 20/411) and membrane (0.9%; n = 12/1360) feeds.ConclusionThe P. vivax IBSM model proved safe and reliable. The clinical course and PMR were reproducible when compared with the previous study using this model. The IBSM model presented in this report shows promise as a system to test transmission-blocking interventions. Further work is required to validate transmission and increase its prevalence.Trial RegistrationAnzctr.org.au ACTRN12613001008718

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Section: Discussionmentioning

confidence: 99%

Safety and Reproducibility of a Clinical Trial System Using Induced Blood Stage Plasmodium vivax Infection and Its Potential as a Model to Evaluate Malaria Transmission

et al. 2016

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“…In diseases such as malaria, human challenge is permitted and can be conducted at a defined time point following immunization (1). For some infectious diseases such as HIV, live human challenge is unethical, so protection is determined through reduced incidence of disease in a susceptible population (2).…”

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confidence: 99%

Immunosignatures can predict vaccine efficacy

Legutki

Johnston

2013

Proc. Natl. Acad. Sci. U.S.A.

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The development of new vaccines would be greatly facilitated by having effective methods to predict vaccine performance. Such methods could also be helpful in monitoring individual vaccine responses to existing vaccines. We have developed "immunosignaturing" as a simple, comprehensive, chip-based method to display the antibody diversity in an individual on peptide arrays. Here we examined whether this technology could be used to develop correlates for predicting vaccine effectiveness. By using a mouse influenza infection, we show that the immunosignaturing of a natural infection can be used to discriminate a protective from nonprotective vaccine. Further, we demonstrate that an immunosignature can determine which mice receiving the same vaccine will survive. Finally, we show that the peptides comprising the correlate signatures of protection can be used to identify possible epitopes in the influenza virus proteome that are correlates of protection.peptide microarray | systems vaccinology | epitope prediction | antibody repertoire | immune profile

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“…Another Phase I/IIa study with recombinant AMA1 delivered in the adjuvants AS01 B and AS02 A also did not show sterilising protection after sporozoite CHMI, but parasite densities seemed to be reduced as estimated from qPCR data (Spring et al, 2009), again suggestive of a possible effect of anti-AMA1 responses at the preerythrocytic stage. A more recent Phase IIa trial of the same vaccine in AS01 B also failed to show any impact on blood-stage PMR of vaccine homologous parasites, following use of the more sensitive blood-stage CHMI model (NCT02044198) (Duncan and Draper, 2012;Sheehy et al, 2013a). Intriguingly, however, this AMA1/AS02 A vaccine was reported to exhibit strain-specific protection in a Phase IIb field trial in Malian children, suggesting efficacy may only be apparent in the context of other naturally acquired responses (Thera et al, 2011).…”

Section: Blood-stage Subunit Vaccinesmentioning

confidence: 87%