Controlled human malaria infection with a clone of Plasmodium vivax with highquality genome assembly

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 Lopej 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

doi:10.1172/jci.insight.152465

Controlled human malaria infection with a clone of Plasmodium vivax with highquality genome assembly

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 MariniMarija Zaric, Margaux Mulatier, Raquel Lopej 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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.

Original language	English
Article number	e152465
Journal	JCI Insight
Volume	6
Issue number	23
DOIs	https://doi.org/10.1172/jci.insight.152465
Publication status	Published - 8 Dec 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021, Minassian et al.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1172/jci.insight.152465

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Minassian, A. M., Themistocleous, Y., Silk, S. E., Barrett, J. R., Kemp, A., Quinkert, D., Nielsen, C. M., Edwards, N. J., Rawlinson, T. A., Lopez, F. R., Roobsoong, W., Ellis, K. J. D., Cho, J. S., Aunin, E., Otto, T. D., Reid, A. J., Bach, F. A., Labbé, G. M. C., Poulton, I. D., ... Draper, S. J. (2021). Controlled human malaria infection with a clone of Plasmodium vivax with highquality genome assembly. JCI Insight, 6(23), Article e152465. https://doi.org/10.1172/jci.insight.152465

@article{0b8f0f99eeda4b8a8f08da143e28f3c6,

title = "Controlled human malaria infection with a clone of Plasmodium vivax with highquality 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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, Minassian et al.",

year = "2021",

month = dec,

day = "8",

doi = "10.1172/jci.insight.152465",

language = "English",

volume = "6",

journal = "JCI Insight",

issn = "2379-3708",

publisher = "American Society for Clinical Investigation",

number = "23",

}

Minassian, AM, Themistocleous, Y, Silk, SE, Barrett, JR, Kemp, A, Quinkert, D, Nielsen, CM, Edwards, NJ, Rawlinson, TA, Lopez, FR, Roobsoong, W, Ellis, KJD, Cho, JS, Aunin, E, Otto, TD, Reid, AJ, Bach, FA, Labbé, GMC, Poulton, ID, Marini, A, Zaric, M, Mulatier, M, Ramon, RL, Baker, M, Mitton, CH, Sousa, JC, Rachaphaew, N, Kumpitak, C, Maneechai, N, Suansomjit, C, Piteekan, T, Hou, MM, Khozoee, B, McHugh, K, Roberts, DJ, Lawrie, AM, Blagborough, AM, Nugent, FL, Taylor, IJ, Johnson, KJ, Spence, PJ, Sattabongkot, J, Biswas, S, Rayner, JC & Draper, SJ 2021, 'Controlled human malaria infection with a clone of Plasmodium vivax with highquality genome assembly', JCI Insight, vol. 6, no. 23, e152465. https://doi.org/10.1172/jci.insight.152465

TY - JOUR

T1 - Controlled human malaria infection with a clone of Plasmodium vivax with highquality 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 - Lopez, Fernando Ramos

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 - Ramon, Raquel Lopej

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 - 2021/12/8

Y1 - 2021/12/8

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 1145 in 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 1145 in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.

UR - http://www.scopus.com/inward/record.url?scp=85120879529&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.152465

DO - 10.1172/jci.insight.152465

M3 - Article

C2 - 34609964

AN - SCOPUS:85120879529

SN - 2379-3708

VL - 6

JO - JCI Insight

JF - JCI Insight

IS - 23

M1 - e152465

ER -

Controlled human malaria infection with a clone of Plasmodium vivax with highquality genome assembly

Abstract

Bibliographical note

UN SDGs

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