Transgenic parasites in malaria

The LUCID malaria research group is at the forefront of international research on malaria vaccine development using live genetically attenuated parasites for immunization. We have developed the GA2-parasite: a P. falciparum attenuated parasite that cannot cause malaria, but can induce protective immunity. Working hand in hand with Dr. Murugan and Prof. Roestenberg's team, we have shown that administration of GA2 in Dutch volunteers through mosquito bites is safe and 90% of the participants was protected against a controlled malaria infection upon GA2-immunizations.

Our research aims  to

• Improve the vaccine potency of GA2, to make a highly efficacious vaccine that can be used to eradicate malaria in endemic  
• Identify and characterize parasite proteins that are (putative) targets for host immune responses.
• Decipher host-pathogen molecular interactions and mechanisms of host-cell remodelling and immune evasion by the parasite, during pre-erythrocytic stages of infection.

The LUCID malaria research group is a world authority on transgenesis in Plasmodium and facilities are available for mouse infection studies, breeding Anopheles stephensi mosquitoes and for mosquito transmission of P. falciparum and rodent malaria parasites.

With our expertise on parasite genome, infection biology and state-of-the-art methodologies, we address fundamental questions impacting future malaria vaccine development.

• Olivia A.C. Lamers, Blandine M.D. Franke-Fayard, Jan Pieter R. Koopman, Geert V. T. Roozen, Jacqueline J. Janse, Severine C. Chevalley-Maurel, Fiona .J.A. Geurten, M. de Bes-Roeleveld, Eva Iliopoulou, Emil .D. Colstrup, Els Wessels, Geert-Jan van Gemert, Marga van de Vegte-Bolmer, Wouter Graumans, Thabitha R. Stoter, Benjamin G. Mordmüller, Emma L. Houlder, Teun Bousema, Rajagopal Murugan, Matthew B.B. McCall, Chris J. Janse, and Meta Roestenberg. (2024). Safety and protection by a late liver-stage attenuated malaria parasite.
• Franke-Fayard B, Marin-Mogollon C, Geurten FJA, Chevalley-Maurel S, Ramesar J, Kroeze H, Baalbergen E, Wessels E, Baron L, Soulard V, Martinson T, Aleshnick M, Huijs ATG, Subudhi AK, Miyazaki Y, Othman AS, Kolli SK, Lamers OAC, Roques M, Stanway RR, Murphy SC, Foquet L, Moita D, Mendes AM, Prudêncio M, Dechering KJ, Heussler VT, Pain A, Wilder BK, Roestenberg M, Janse CJ. (2022). Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver. NPJ Vaccines Nov 4;7(1):139. DOI: 10.1038/s41541-022-00558-x
• Fougère A, Jackson AP, Paraskevi Bechtsi D, Braks JA, Annoura T, Fonager J, Spaccapelo R, Ramesar J, Chevalley-Maurel S, Klop O, van der Laan AM, Tanke HJ, Kocken CH, Pasini EM, Khan SM, Böhme U, van Ooij C, Otto TD, Janse CJ, Franke-Fayard B. (2016) Variant Exported Blood-Stage Proteins Encoded by Plasmodium Multigene Families Are Expressed in Liver Stages Where They Are Exported into the Parasitophorous Vacuole. PLoS Pathog. Nov 16;12(11). DOI: 10.1371/journal.ppat.1005917
• Fonager, J., Pasini, E. M., Braks, J. A., Klop, O., Ramesar, J., Remarque, E. J., Vroegrijk, I. O., van Duinen, S. G., Thomas, A. W., Khan, S. M., Mann, M., Kocken, C. H., Janse, C. J. & Franke-Fayard, B. M. (2012). Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo. J. Exp. Med. 209, 93-107.
• Franke-Fayard,B.^##, Trueman,H., Ramesar,J., Mendoza,J., Van Der,K.M., Van Der,L.R., Sinden,R.E., Waters,A.P. and Janse,C.J. (2004) A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle. Mol. Biochem. Parasitol. 137, 23-33.