Controlled Human Malaria Infection with a Clone of Plasmodium Vivax with High-quality Genome Assembly

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.

Citing Articles

Assembled genome of an Ethiopian isolate generated using GridION long-read technology.

Callejas-Hernandez F, Nikulkova M, Adamski N, Yan G, Yewhalaw D, Carlton J Microbiol Resour Announc. 2024; 13(10):e0059024.

PMID: 39283158 PMC: 11465822. DOI: 10.1128/mra.00590-24.

Evaluation of the precision of the Plasmodium knowlesi growth inhibition assay for Plasmodium vivax Duffy-binding protein-based malaria vaccine development.

Mertens J, Rigby C, Bardelli M, Quinkert D, Hou M, Diouf A Vaccine. 2024; 42(16):3621-3629.

PMID: 38704253 PMC: 11128340. DOI: 10.1016/j.vaccine.2024.04.073.

Population genomic evidence of structured and connected populations under host selection in Latin America.

Kattenberg J, Monsieurs P, De Meyer J, De Meulenaere K, Sauve E, de Oliveira T Ecol Evol. 2024; 14(3):e11103.

PMID: 38529021 PMC: 10961478. DOI: 10.1002/ece3.11103.

Analyses of human vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens.

Barrett J, Silk S, Mkindi C, Kwiatkowska K, Hou M, Lias A Front Immunol. 2024; 14:1193079.

PMID: 38299155 PMC: 10827869. DOI: 10.3389/fimmu.2023.1193079.

PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial.

Martinez F, White M, Guillotte-Blisnick M, Huon C, Boucharlat A, Agou F NPJ Vaccines. 2024; 9(1):10.

PMID: 38184681 PMC: 10771494. DOI: 10.1038/s41541-023-00796-7.

References

Galinski M, Barnwell J . Plasmodium vivax: who cares?. Malar J. 2008; 7 Suppl 1:S9. PMC: 2604873. DOI: 10.1186/1475-2875-7-S1-S9. View

Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M . Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. J Infect Dis. 2008; 198(10):1558-64. PMC: 4337975. DOI: 10.1086/592451. View

Payne R, Silk S, Elias S, Milne K, Rawlinson T, Llewellyn D . Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight. 2017; 2(12). PMC: 5470884. DOI: 10.1172/jci.insight.93683. View

Rebsamen M, Desmeules J, Daali Y, Chiappe A, Diemand A, Rey C . The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction. Pharmacogenomics J. 2008; 9(1):34-41. DOI: 10.1038/tpj.2008.7. View

Odedra A, Webb L, Marquart L, Britton L, Chalon S, Moehrle J . Liver Function Test Abnormalities in Experimental and Clinical Infection. Am J Trop Med Hyg. 2020; 103(5):1910-1917. PMC: 7646782. DOI: 10.4269/ajtmh.20-0491. View

Alkema M, Reuling I, de Jong G, Lanke K, Coffeng L, van Gemert G . Corrigendum to: A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite-Induced Controlled Malaria Infection. J Infect Dis. 2020; 222(8):1416. PMC: 7488196. DOI: 10.1093/infdis/jiaa428. View

Kamau E, Bennett J, Yadava A . Safety and Tolerability of Mosquito Bite-Induced Controlled Human Infection with Plasmodium vivax in Malaria-Naive Study Participants-Clinical Profile and Utility of Molecular Diagnostic Methods. J Infect Dis. 2021; 225(1):146-156. DOI: 10.1093/infdis/jiab332. View

Carlton J, Adams J, Silva J, Bidwell S, Lorenzi H, Caler E . Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature. 2008; 455(7214):757-63. PMC: 2651158. DOI: 10.1038/nature07327. View

Stanisic D, McCarthy J, Good M . Controlled Human Malaria Infection: Applications, Advances, and Challenges. Infect Immun. 2017; 86(1). PMC: 5736798. DOI: 10.1128/IAI.00479-17. View

10.

Arevalo-Herrera M, Forero-Pena D, Rubiano K, Gomez-Hincapie J, Martinez N, Lopez-Perez M . Plasmodium vivax sporozoite challenge in malaria-naïve and semi-immune Colombian volunteers. PLoS One. 2014; 9(6):e99754. PMC: 4070897. DOI: 10.1371/journal.pone.0099754. View

11.

Popovici J, Roesch C, Carias L, Khim N, Kim S, Vantaux A . Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity. Nat Commun. 2020; 11(1):953. PMC: 7031336. DOI: 10.1038/s41467-020-14574-9. View

12.

Harrison T, Morch A, Felce J, Sakoguchi A, Reid A, Arase H . Structural basis for RIFIN-mediated activation of LILRB1 in malaria. Nature. 2020; 587(7833):309-312. PMC: 7116854. DOI: 10.1038/s41586-020-2530-3. View

13.

Suwanarusk R, Russell B, Chavchich M, Chalfein F, Kenangalem E, Kosaisavee V . Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms. PLoS One. 2007; 2(10):e1089. PMC: 2034531. DOI: 10.1371/journal.pone.0001089. View

14.

Duncan C, Draper S . Controlled human blood stage malaria infection: current status and potential applications. Am J Trop Med Hyg. 2012; 86(4):561-5. PMC: 3403771. DOI: 10.4269/ajtmh.2012.11-0504. View

15.

Bright A, Manary M, Tewhey R, Arango E, Wang T, Schork N . A high resolution case study of a patient with recurrent Plasmodium vivax infections shows that relapses were caused by meiotic siblings. PLoS Negl Trop Dis. 2014; 8(6):e2882. PMC: 4046966. DOI: 10.1371/journal.pntd.0002882. View

16.

Chen N, Auliff A, Rieckmann K, Gatton M, Cheng Q . Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervals. J Infect Dis. 2007; 195(7):934-41. DOI: 10.1086/512242. View

17.

White N . Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J. 2011; 10:297. PMC: 3228849. DOI: 10.1186/1475-2875-10-297. View

18.

Pearson R, Amato R, Auburn S, Miotto O, Almagro-Garcia J, Amaratunga C . Genomic analysis of local variation and recent evolution in Plasmodium vivax. Nat Genet. 2016; 48(8):959-964. PMC: 4966634. DOI: 10.1038/ng.3599. View

19.

Pornthanakasem W, Riangrungroj P, Chitnumsub P, Ittarat W, Kongkasuriyachai D, Uthaipibull C . Role of Plasmodium vivax Dihydropteroate Synthase Polymorphisms in Sulfa Drug Resistance. Antimicrob Agents Chemother. 2016; 60(8):4453-63. PMC: 4958149. DOI: 10.1128/AAC.01835-15. View

20.

Rice B, Acosta M, Pacheco M, Carlton J, Barnwell J, Escalante A . The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites. Mol Phylogenet Evol. 2014; 78:172-84. PMC: 4406276. DOI: 10.1016/j.ympev.2014.05.013. View