Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly
Angela M. Minassian, et al.
Angela M. Minassian, et al.
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Resource and Technical Advance Infectious disease

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

Abstract

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.

Authors

Angela M. Minassian, Yrene Themistocleous, Sarah E. Silk, Jordan R. Barrett, Alison Kemp, Doris Quinkert, Carolyn M. Nielsen, Nick J. Edwards, Thomas A. Rawlinson, Fernando Ramos Lopez, Wanlapa Roobsoong, Katherine J.D. Ellis, Jee-Sun Cho, Eerik Aunin, Thomas D. Otto, Adam J. Reid, Florian A. Bach, Geneviève M.C. Labbé, Ian D. Poulton, Arianna Marini, Marija Zaric, Margaux Mulatier, Raquel Lopez Ramon, Megan Baker, Celia H. Mitton, Jason C. Sousa, Nattawan Rachaphaew, Chalermpon Kumpitak, Nongnuj Maneechai, Chayanut Suansomjit, Tianrat Piteekan, Mimi M. Hou, Baktash Khozoee, Kirsty McHugh, David J. Roberts, Alison M. Lawrie, Andrew M. Blagborough, Fay L. Nugent, Iona J. Taylor, Kimberly J. Johnson, Philip J. Spence, Jetsumon Sattabongkot, Sumi Biswas, Julian C. Rayner, Simon J. Draper

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Figure 2

Test of cryopreserved parasite viability by short-term in vitro culture assay.

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Test of cryopreserved parasite viability by short-term in vitro culture ...
(A) Test vials of cryopreserved parasites from Donor 1 and Donor 2 were thawed, and cells were used in a short-term in vitro parasite culture assay. P. vivax parasite growth was monitored by qPCR in 20 μL samples of RBC extracted at the indicated time points. Median and range of triplicate readings are shown in genome copies measured per 20 μL sample. (B) Parasite morphology was monitored at the same time points over the first growth cycle by light microscopy of Giemsa-stained thick and thin blood films Representative images are shown from Donor 1, and the predominant morphology observed is reported. Total original magnification, ×1000.