Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.

Autor:	Payne RO; Jenner Institute Laboratories Centre for Clinical Vaccinology and Tropical Medicine., Milne KH; Jenner Institute Laboratories., Elias SC; Jenner Institute Laboratories., Edwards NJ; Jenner Institute Laboratories., Douglas AD; Jenner Institute Laboratories., Brown RE; Jenner Institute Laboratories., Silk SE; Jenner Institute Laboratories., Biswas S; Jenner Institute Laboratories., Miura K; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda., Roberts R; Centre for Clinical Vaccinology and Tropical Medicine., Rampling TW; Jenner Institute Laboratories Centre for Clinical Vaccinology and Tropical Medicine., Venkatraman N; Jenner Institute Laboratories Centre for Clinical Vaccinology and Tropical Medicine., Hodgson SH; Jenner Institute Laboratories Centre for Clinical Vaccinology and Tropical Medicine., Labbé GM; Jenner Institute Laboratories., Halstead FD; Jenner Institute Laboratories., Poulton ID; Centre for Clinical Vaccinology and Tropical Medicine., Nugent FL; Jenner Institute Laboratories., de Graaf H; National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility, University Hospital Southampton National Health Service (NHS) Foundation Trust Faculty of Medicine, University of Southampton., Sukhtankar P; National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility, University Hospital Southampton National Health Service (NHS) Foundation Trust Faculty of Medicine, University of Southampton., Williams NC; Centre for Statistics in Medicine Botnar Research Centre, University of Oxford., Ockenhouse CF; Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland PATH Malaria Vaccine Initiative., Kathcart AK; Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland., Qabar AN; Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland., Waters NC; Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland., Soisson LA; US Agency for International Development, Washington D.C., Birkett AJ; PATH Malaria Vaccine Initiative., Cooke GS; NIHR Wellcome Trust Clinical Research Facility, Imperial College Healthcare NHS Trust, London, United Kingdom., Faust SN; National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility, University Hospital Southampton National Health Service (NHS) Foundation Trust Faculty of Medicine, University of Southampton., Woods C; PATH Malaria Vaccine Initiative., Ivinson K; PATH Malaria Vaccine Initiative., McCarthy JS; QIMR Berghofer Medical Research Institute, Herston, Australia., Diggs CL; US Agency for International Development, Washington D.C., Vekemans J; GlaxoSmithKline Vaccines, Rixensart, Belgium., Long CA; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda., Hill AV; Jenner Institute Laboratories., Lawrie AM; Centre for Clinical Vaccinology and Tropical Medicine., Dutta S; Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland., Draper SJ; Jenner Institute Laboratories.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2016 Jun 01; Vol. 213 (11), pp. 1743-51. Date of Electronic Publication: 2016 Feb 04.
DOI:	10.1093/infdis/jiw039
Abstrakt:	Background: Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P. falciparum CHMI model to assess blood-stage vaccine candidates, using their impact on the parasite multiplication rate (PMR) as the primary efficacy end point. Methods: Fifteen healthy United Kingdom adult volunteers were vaccinated with FMP2.1, a protein vaccine that is based on the 3D7 clone sequence of apical membrane antigen 1 (AMA1) and formulated in Adjuvant System 01 (AS01). Twelve vaccinees and 15 infectivity controls subsequently underwent blood-stage CHMI. Parasitemia was monitored by quantitative real-time polymerase chain reaction (PCR) analysis, and PMR was modeled from these data. Results: FMP2.1/AS01 elicited anti-AMA1 T-cell and serum antibody responses. Analysis of purified immunoglobulin G showed functional growth inhibitory activity against P. falciparum in vitro. There were no vaccine- or CHMI-related safety concerns. All volunteers developed blood-stage parasitemia, with no impact of the vaccine on PMR. Conclusions: FMP2.1/AS01 demonstrated no efficacy after blood-stage CHMI. However, the model induced highly reproducible infection in all volunteers and will accelerate proof-of-concept testing of future blood-stage vaccine candidates. Clinical Trials Registration: NCT02044198. (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
Databáze:	MEDLINE
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