Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly.

Autor: Minassian AM; The Jenner Institute and., Themistocleous Y; The Jenner Institute and., Silk SE; The Jenner Institute and.; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Barrett JR; The Jenner Institute and.; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Kemp A; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom.; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Quinkert D; The Jenner Institute and.; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Nielsen CM; The Jenner Institute and.; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Edwards NJ; The Jenner Institute and., Rawlinson TA; The Jenner Institute and., Ramos Lopez F; The Jenner Institute and., Roobsoong W; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Ellis KJ; The Jenner Institute and., Cho JS; The Jenner Institute and., Aunin E; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom., Otto TD; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom., Reid AJ; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom., Bach FA; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom., Labbé GM; The Jenner Institute and., Poulton ID; The Jenner Institute and., Marini A; The Jenner Institute and., Zaric M; The Jenner Institute and., Mulatier M; The Jenner Institute and., Lopez Ramon R; The Jenner Institute and., Baker M; The Jenner Institute and., Mitton CH; The Jenner Institute and., Sousa JC; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Rachaphaew N; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Kumpitak C; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Maneechai N; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Suansomjit C; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Piteekan T; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Hou MM; The Jenner Institute and., Khozoee B; The Jenner Institute and., McHugh K; The Jenner Institute and.; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Roberts DJ; Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Lawrie AM; The Jenner Institute and., Blagborough AM; Department of Pathology, University of Cambridge, Cambridge, United Kingdom., Nugent FL; The Jenner Institute and., Taylor IJ; The Jenner Institute and., Johnson KJ; The Jenner Institute and., Spence PJ; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom., Sattabongkot J; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Biswas S; The Jenner Institute and., Rayner JC; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom.; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Draper SJ; The Jenner Institute and.; Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2021 Dec 08; Vol. 6 (23). Date of Electronic Publication: 2021 Dec 08.
DOI: 10.1172/jci.insight.152465
Abstrakt: Controlled human malaria infection (CHMI) provides a highly informative means to investigate host-pathogen interactions and enable in vivo proof-of-concept efficacy testing of new drugs and vaccines. However, unlike Plasmodium falciparum, well-characterized P. vivax parasites that are safe and suitable for use in modern CHMI models are limited. Here, 2 healthy malaria-naive United Kingdom adults with universal donor blood group were safely infected with a clone of P. vivax from Thailand by mosquito-bite CHMI. Parasitemia developed in both volunteers, and prior to treatment, each volunteer donated blood to produce a cryopreserved stabilate of infected RBCs. Following stringent safety screening, the parasite stabilate from one of these donors (PvW1) was thawed and used to inoculate 6 healthy malaria-naive United Kingdom adults by blood-stage CHMI, at 3 different dilutions. Parasitemia developed in all volunteers, who were then successfully drug treated. PvW1 parasite DNA was isolated and sequenced to produce a high-quality genome assembly by using a hybrid assembly method. We analyzed leading vaccine candidate antigens and multigene families, including the vivax interspersed repeat (VIR) genes, of which we identified 1145 in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.
Databáze: MEDLINE