Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers

Lawrence, Gregory J.; Cheng, Qin; Reed, Christie; Taylor, Darrin; Stowers, Anthony W.; Cloonan, Nicole; Rzepczyk, Christine M.; Smillie, Anne; Anderson, Karen; Pombo, David; Allworth, Anthony; Eisen, Damon P.; Anders, Robin F.; Saul, Allan

doi:10.1016/s0264-410x(99)00444-2

Cited by 132 publications

(139 citation statements)

References 6 publications

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“…However, the inhibition of merozoite invasion obtained with monoclonal antibodies has not been induced to date by immunisation. [36][37][38] Several other molecules are being channelled into human trials on the basis of results considered promising and obtained in one of the primate, mouse, or in-vitro models (figure 1). [39][40][41][42][43] Clinical trials will be essential to show whether these results can be extended to human beings.…”

Section: Personal Viewmentioning

confidence: 99%

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Guérin¹,

Olliaro

Nosten

et al. 2002

The Lancet Infectious Diseases

317

201

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Section: Personal Viewmentioning

confidence: 99%

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Guérin¹,

Olliaro

Nosten

et al. 2002

The Lancet Infectious Diseases

317

201

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“…ISA-720 has been evaluated with malaria antigens in several small-scale human clinical trials where the safety profiles were acceptable. [32][33][34] Saponins, such as QS-21 35 induce mixed immune responses with both antibody and cellular components. 36 QS-21 in combination with mono phosphoryl lipid A and an oil-in-water emulsion forms the proprietary adjuvant ASO2.…”

Section: Human Vaccines 19mentioning

confidence: 99%

Development, Characterization and Immunogenicity of a Multi-Stage, MultivalentPlasmodium falciparumVaccine Antigen (FALVAC-1A) Expressed inEscherichia coli

Zhou¹,

Todd²,

Wohlhueter³

et al. 2006

Human Vaccines

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A synthetic multistage, multi-epitope Plasmodium falciparum malaria antigen (FALVAC-1A) was designed and evaluated in silico, and then the gene was constructed and expressed in Escherichia coli. The FALVAC-1A protein was purified by inclusion body isolation, followed by affinity and ion exchange chromatography. Although FALVAC-1A was a synthetic antigen, it folded to a specific, but as yet incompletely defined, molecular conformation that was stable and comparable from lot to lot. When formulated with four different adjuvants, FALVAC-1A was highly immunogenic in rabbits, inducing not only ELISA reactivity to the cognate antigen and most of its component epitopes, but also in vitro activity against P. falciparum parasites as demonstrated by inhibition of sporozoite invasion, antibody dependent cellular inhibition and the immunofluorescence assay.

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“…However postthaw viability of the parasite stock varies widely (10-100%). This finding does not appear to be related to duration of storage, but may be caused by sensitivity of the parasites to freeze-thaw procedures and storage conditions, 9 and the current lack of an agreed or standardized viability assay.…”

Section: Controlled Human Blood Stage Malaria Infectionmentioning

confidence: 87%

“…4 Intravenous injection of a sterile suspension of thawed leukocyte-depleted erythrocytes, combined with monitoring of parasitemia postinoculation by highly-sensitive quantitative polymerase chain reaction (qPCR), enables accurate calculation of in vivo parasite multiplication rates (PMRs), a surrogate end-point for vaccine efficacy testing. 4,[6][7][8][9] The inoculum, estimated from the pre-freeze donor parasitemia, is retrospectively quantified by testing viability of the thawed stock. 4 Volunteers in BSP CHMIs were typically treated at a pre-defined parasite density predicted to prevent clinical malaria, 4,9,10 although more recent studies have used the onset of microscopic patency as a treatment endpoint.…”

Section: Controlled Human Blood Stage Malaria Infectionmentioning

confidence: 99%

“…Fifty-nine volunteers have been infected in this manner by using the same frozen starting material, 4,6,[9][10][11][12] extending the safety database for this parasite stock. There is an extremely low risk of blood-borne virus transmission because of stringent screening of the original donor, and requirements for seropositivity for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in recipients (because of donor seropositivity).…”

Section: Controlled Human Blood Stage Malaria Infectionmentioning

confidence: 99%

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

Duncan¹,

Draper²

2012

The American Journal of Tropical Medicine and Hygiene

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Abstract. Controlled human malaria infection by blood stage parasite (BSP) inoculation is an alternative to the wellestablished model of infection with Plasmodium falciparum sporozoites delivered by mosquito bites. The BSP model has been utilized less frequently, but its use is increasing. Advantages of BSP challenge include greater ease of administration, better standardization of the infecting dose per volunteer, and good inter-study reproducibility of in vivo parasite dynamics. Recently, a surprising reduction in clinical symptoms at microscopic patency in the BSP model has been identified, which has an undefined and intriguing pathophysiologic basis, but may make this approach more acceptable to volunteers. We summarize clinical, parasitologic, and immunologic data from all BSP challenges to date, explore differences between the BSP and sporozoite models, and propose future applications for BSP challenge.

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Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers

Cited by 132 publications

References 6 publications

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Development, Characterization and Immunogenicity of a Multi-Stage, MultivalentPlasmodium falciparumVaccine Antigen (FALVAC-1A) Expressed inEscherichia coli

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

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