Malaria

The malaria program grounds on non-human primate (NHP) models and investigates parasite-host (cell) interactions at the molecular level. In our studies we focus on NHP malaria parasites that are zoonotic, as well as on human malaria parasites. We use parasite transfection and OMIC-approaches for global response analyses as a basis for developing improved human vaccine and drug therapies. First- and second-generation vaccine candidates, based on the apical membrane antigen-1 and integrating a novel diversity-covering (DiCo) approach, were developed until the stage of clinical testing. This work included safety and immunogenicity evaluation of vaccine formulations in NHP and provided substantial expertise in recombinant protein production, vaccine formulation and immunological assay harmonization. Next to models for in vivo and in vitro assessment of drug efficacy against blood stage malaria, we have developed a novel ex vivo hepatocyte culture system for low- to medium-throughput drug screening against (dormant) liver stages of malaria. Data acquisition is with a (confocal) high-content high-throughput imager (Operetta®) assuring data quality. This complements an in vivo drug/vaccine efficacy model in NHP to address (dormant) liver infections of NHP malaria with identical biology to human malaria.

Selected References

Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.
Mahdi Abdel Hamid M, Remarque EJ, van Duivenvoorde LM, van der Werff N, Walraven V, Faber BW, Kocken CH, Thomas AW.
PLoS One. 2011;6(5):e20547. doi: 10.1371/journal.pone.0020547.

Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naïve adults.
Remarque EJ, Roestenberg M, Younis S, Walraven V, van der Werff N, Faber BW, Leroy O, Sauerwein R, Kocken CH, Thomas AW.
PLoS One. 2012;7(6):e38898. doi: 10.1371/journal.pone.0038898.

Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo.
Fonager J, Pasini EM, Braks JA, Klop O, Ramesar J, Remarque EJ, Vroegrijk IO, van Duinen SG, Thomas AW, Khan SM, Mann M, Kocken CH, Janse CJ, Franke-Fayard BM.
J Exp Med. 2012 Jan 16;209(1):93-107. doi: 10.1084/jem.20110762

Transgenic fluorescent Plasmodium cynomolgi liver stages enable live imaging and purification of Malaria hypnozoite-forms.
Voorberg-van der Wel A, Zeeman AM, van Amsterdam SM, van den Berg A, Klooster EJ, Iwanaga S, Janse CJ, van Gemert GJ, Sauerwein R, Beenhakker N, Koopman G, Thomas AW, Kocken CH.
PLoS One. 2013;8(1):e54888. doi: 10.1371/journal.pone.0054888.

KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.
Zeeman AM, van Amsterdam SM, McNamara CW, Voorberg-van der Wel A, Klooster EJ, van den Berg A, Remarque EJ, Plouffe DM, van Gemert GJ, Luty A, Sauerwein R, Gagaring K, Borboa R, Chen Z, Kuhen K, Glynne RJ, Chatterjee AK, Nagle A, Roland J, Winzeler EA, Leroy D, Campo B, Diagana TT, Yeung BK, Thomas AW, Kocken CH.
Antimicrob Agents Chemother. 2014;58(3):1586-95. doi: 10.1128/AAC.01927-13.

Persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures.
Dembélé L, Franetich JF, Lorthiois A, Gego A, Zeeman AM, Kocken CH, Le Grand R, Dereuddre-Bosquet N, van Gemert GJ, Sauerwein R, Vaillant JC, Hannoun L, Fuchter MJ, Diagana TT, Malmquist NA, Scherf A, Snounou G, Mazier D.
Nat Med. 2014 Mar;20(3):307-12. doi: 10.1038/nm.3461.

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