TY - JOUR
T1 - Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly
AU - Minassian, Angela M.
AU - Themistocleous, Yrene
AU - Silk, Sarah E.
AU - Barrett, Jordan R.
AU - Kemp, Alison
AU - Quinkert, Doris
AU - Nielsen, Carolyn M.
AU - Edwards, Nick J.
AU - Rawlinson, Thomas A.
AU - Ramos Lopez, Fernando
AU - Roobsoong, Wanlapa
AU - Ellis, Katherine J.D.
AU - Cho, Jee-Sun
AU - Aunin, Eerik
AU - Otto, Thomas D.
AU - Reid, Adam J.
AU - Bach, Florian A.
AU - Labbé, Geneviève M.C.
AU - Poulton, Ian D.
AU - Marini, Arianna
AU - Zaric, Marija
AU - Mulatier, Margaux
AU - Lopez Ramon, Raquel
AU - Baker, Megan
AU - Mitton, Celia H.
AU - Sousa, Jason C.
AU - Rachaphaew, Nattawan
AU - Kumpitak, Chalermpon
AU - Maneechai, Nongnuj
AU - Suansomjit, Chayanut
AU - Piteekan, Tianrat
AU - Hou, Mimi M.
AU - Khozoee, Baktash
AU - McHugh, Kirsty
AU - Roberts, David J.
AU - Lawrie, Alison M.
AU - Blagborough, Andrew M.
AU - Nugent, Fay L.
AU - Taylor, Iona J.
AU - Johnson, Kimberly J.
AU - Spence, Philip J.
AU - Sattabongkot, Jetsumon
AU - Biswas, Sumi
AU - Rayner, Julian C.
AU - Draper, Simon J.
PY - 2021/10/5
Y1 - 2021/10/5
N2 - 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 1145in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.
AB - 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 1145in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.
U2 - 10.1172/jci.insight.152465
DO - 10.1172/jci.insight.152465
M3 - Article
SN - 2379-3708
VL - 6
JO - JCI Insight
JF - JCI Insight
IS - 23
M1 - e152465
ER -