- Malaria (Parasitology)
- Vaccine development
- Cell and Molecular Biology
Head of the Leiden Malaria Research Group (Associate Professor)
Department of Parasitology, Center of Infectious Diseases
- Development of a malaria vaccine based on genetically attenuated parasites
- Identification and analysis of parasite proteins that are (putative) targets for subunit vaccines
- Identification and analysis of parasite proteins that are (putative) targets for drugs
- Analysis of parasite-host interactions involved in pathology and disease
Website of the Leiden Malaria Research Group
The Leiden Malaria Group (LMRG) developed Plasmodium genetic modification in 1995 and continues to innovate and lead research into Plasmodium transgenesis. Gene deletion mutants generated have been used to analyze a wide range of parasite gene functions. In 2005 they were one of the first groups to create genetically attenuated parasites that could serve as a live-parasite vaccine against malaria. In addition to gene-deletion and disruption-mutants, LMRG has created a number of parasites expressing foreign ‘transgenes’ to create reference parasite lines including those expressing fluorescent, bioluminescent, OVA reporter proteins, which have proven to be valuable tools in dissecting parasite-host interactions at the cellular and molecular level and shared by many different labs world-wide. They have created over 160 transgene expressing mutants and have distributed various mutant- and transgenic lines to more than 50 groups across the world.
Recently, the LMRG applied their expertise of Plasmodium genetic modification to the human parasite P. falciparum and developed a novel method to efficiently generate stable genetically modified Pf that are free of heterologous drug selectable markers facilitating sequential genetic modifications. This method is key in creating a genetically attenuated PfSPZ vaccine (GAP vaccine), developed in collaboration with Sanaria, which has gained regulatory approval and will be tested in volunteers in 2017. As with rodent malaria parasites the LMRG, has developed technologies to not only remove genes from the parasite genome but have also insert transgenes into the human parasite. The LMRG have further refined the recently described CRISPR-Cas9 genetic modification method in P. falciparum to more rapidly create mutant (gene deletion and insertion) parasite lines, free of genes encoding drug resistance proteins.
The Leiden Malaria SharePoint Resource Center provides general information about the Plasmodium berghei rodent model of malaria. It contains detailed protocols for biological assays, molecular techniques and information about our standard ‘in-house’ plasmids for a variety of genetic modifications in rodent malaria parasites. In addition, the website also provides databases (Excel files) with transcriptome, proteome and genome data. A significant number of standard plasmids for genetic modification and transgenic P. berghei parasite lines from the Leiden Malaria Group are available to the malaria research community.
www.pberghei.eu is a web-based database (RMgmDB) from the Leiden Malaria Group containing information on genetically modified rodent malaria parasite lines generated by many labs worldwide. Specifically, it contains data of three rodent malaria parasite species; Plasmodium berghei, P. yoelii and P. chabaudi. The aim of this database is to provide the research community access to detailed information on the generation (e.g. disruption, tagging, mutation, transgene expression) and phenotype of genetically modified malaria parasites. The information in this database is shared with the ‘Sanger Institute Pathogen Genome Database’ (www.GeneDB.org) and ‘EuPathDB Bioinformatics Resource Center for biodefense and Emerging / Re-emerging Infectious Diseases’ (www.PlasmoDB.org)
Dijk, M.R. van, Waters, A.P. and Janse, C.J. (1995). Stable transfection of malaria parasite blood stages. Science 268, 1358-1362.
Dijk, M.R. van, Janse, C.J. and Waters, A.P. (1996). Expression of a Plasmodium gene introduced into subtelomeric regions of Plasmodium berghei chromosomes. Science 271, 662-665.
Wel, A.M. van der, Tomas, A.M., Kocken, C.H.M., Malhotrall, P., Janse, C.J., Waters, A.P. and A.W. Thomas (1997). Transfection of the primate malaria parasite Plasmodium knowlesi using entirely heterologous constructs. J.Exp.Med. 185, 1499-1503
Menard, R., Sultan, A.A., Cortes, C., Altszuler, R., van Dijk, M.R., Janse, C.J., Waters, A.P., Nussenzweig, R.S. and Nussenzweig, V. (1997). Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature 385, 336-340.
Wengelnik, K., Spaccapelo, R., Naitza, S., Robson, K.J.H., Janse, C.J., Waters, A.P. & Crisanti, A. (1999). TRAP complementation in Plasmodium berghei and mutation analysis reveals a role of the conserved adhesive domains in the invasion of mosquito salivary glands. EMBO J. 18, 5195-204
Tomas, A.M., Margos, G., Dimopoulos, G., Lin, L.H.M. van, de Koning-Ward, T.F., Sinha, R., Lupetti, P., Beetsma, A.L., Rodriguez, M.C., Karras, M., Hagar, A., Mendoza, J., Butcher, G.A., Kafatos, F.C., Janse, C.J., Waters, A.P. and Sinden, R.E. (2001). The conserved P25/P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO Journal 20, 3975-83.
Dijk, M.R., Janse, C.J., Thompson, J., Waters, A.P., Braks, J.A.M., Dodemont, H.J., Stunnenberg, H.G., Gemert, G.J. van, Sauerwein, R.W. and Eling, W. (2001). A central role for P48/45 in malaria parasite male gamete fertility. Cell 104, 153-164
Carlton JM, Angiuoli SV, Suh BB, Kooij TW, Pertea M, Silva JC, Ermolaeva MD, Allen JE, Selengut JD, Koo HL, Peterson JD, Pop M, Kosack DS, Shumway MF, Bidwell SL, Shallom SJ, van Aken SE, Riedmuller SB, Feldblyum TV, Cho JK, Quackenbush J, Sedegah M, Shoaibi A, Cummings LM, Florens L, Yates JR, Raine JD, Sinden RE, Harris MA, Cunningham DA, Preiser PR, Bergman LW, Vaidya AB, van Lin LH, Janse CJ, Waters AP, Smith HO, White OR, Salzberg SL, Venter JC, Fraser CM, Hoffman SL, Gardner MJ, Carucci DJ. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature. 2002, 419:512-9.
Blandin S, Shiao SH, Moita LF, Janse CJ, Waters AP, Kafatos FC, Levashina EA (2004) Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell. 116: 661-70.
Kooij TW, Carlton JM, Bidwell SL, Hall N, Ramesar J, Janse CJ, Waters AP (2005) A Plasmodium Whole-Genome Synteny Map: Indels and Synteny Breakpoints as Foci for Species-Specific Genes. PLoS Pathog. 23;1(4): e44
van Dijk MR, Douradinha B, Franke-Fayard B, Heussler V, van Dooren MW, van Schaijk B, van Gemert GJ, Sauerwein RW, Mota MM, Waters AP, Janse CJ. (2005). Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proc Natl Acad Sci U S A, 102:12194-9
Franke-Fayard B, Janse CJ, Cunha-Rodrigues M, Ramesar J, Buscher P, Que I, Lowik C, Voshol PJ, den Boer MA, van Duinen SG, Febbraio M, Mota MM, Waters AP.(2005). Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc Natl Acad Sci U S A. 102. 11468-73
Khan, S.M., Franke-Fayard, B., Mair, G.R., Lasonder, E., Janse, C.J, Mann, M. & Waters, A.P. (2005) Proteome analysis of separated male and female gametocytes reveals novel sex specific Plasmodium biology. Cell 121: 675-87
Hall, N., Karras, M., Raine, J.D., Carlton, J.M., Kooij, T.W.A., Berriman, M., Florens, L., Janssen, C., Pain, A., Christophides, C.K., James, K., Rutherford, K., Harris, B., Harris, D., Churcher, C., Quail, M.A., Ormond, D., Doggett, J., Trueman, H.E., Mendoza, J., Bidwell, S., Rajandream, M.A., Carucci, D.A., Yates, J.R. III, Kafatos, F.C., Janse, C.J., Barrell, B., Turner, C.M.R., Waters, A.P., Sinden, R.E. (2005) A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic and proteomic analyses. Science 307. 82-6.
Waters, A.P. Mota, M.M., van Dijk, M.R. & Janse C.J. (2005) Malaria Vaccines: Back to the Future? – Perspective. Science 307:528-30
Mair GR, Braks JA, Garver LS, Wiegant JC, Hall N, Dirks RW, Khan SM, Dimopoulos G, Janse CJ, Waters AP (2006). Regulation of sexual development of Plasmodium by translational repression. Science 313: 667-9.
Kooij TW, Janse CJ, Waters AP (2006). Plasmodium post-genomics: better the bug you know? Nat Rev Microbiol. 4: 344-57. Review.
Janse CJ, Franke-Fayard B, Waters AP. Selection by flow-sorting of genetically transformed, GFP-expressing blood stages of the rodent malaria parasite, Plasmodium berghei. Nat Protoc. 2006;1(2):614-23.
Franke-Fayard B, Waters AP, Janse CJ. Real-time in vivo imaging of transgenic bioluminescent blood stages of rodent malaria parasites in mice. Nat Protoc. 2006;1(1):476-85.
Janse CJ, Ramesar J, Waters AP. High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei. Nat Protoc. 2006;1(1):346-56.
van Ooij C, Tamez P, Bhattacharjee S, Hiller NL, Harrison T, Liolios K, Kooij T, Ramesar J, Balu B, Adams J, Waters A, Janse C, Haldar K. The malaria secretome: from algorithms to essential function in blood stage infection. PLoS Pathog. 2008 Jun 13;4(6):e1000084.
Lasonder E, Janse CJ, van Gemert GJ, Mair GR, Vermunt AM, Douradinha BG, van Noort V, Huynen MA, Luty AJ, Kroeze H, Khan SM, Sauerwein RW, Waters AP, Mann M, Stunnenberg HG. Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity. PLoS Pathog. 2008 Oct;4(10):e1000195.
Yu M, Kumar TR, Nkrumah LJ, Coppi A, Retzlaff S, Li CD, Kelly BJ, Moura PA, Lakshmanan V, Freundlich JS, Valderramos JC, Vilcheze C, Siedner M, Tsai JH, Falkard B, Sidhu AB, Purcell LA, Gratraud P, Kremer L, Waters AP, Schiehser G, Jacobus DP, Janse CJ, Ager A, Jacobs WR Jr, Sacchettini JC, Heussler V, Sinnis P, Fidock DAThe fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.. Cell Host Microbe. 2008 4:567-78.
Vega-Rodríguez J, Franke-Fayard B, Dinglasan RR, Janse CJ, Pastrana-Mena R, Waters AP, Coppens I, Rodríguez-Orengo JF, Jacobs-Lorena M, Serrano AE. The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission. PLoS Pathog. 2009, 5(2):e1000302.
Baum J, Papenfuss AT, Mair GR, Janse CJ, Vlachou D, Waters AP, Cowman AF, Crabb BS, de Koning-Ward TF. Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res. 2009;37(11):3788-98.
Moon RW, Taylor CJ, Bex C, Schepers R, Goulding D, Janse CJ, Waters AP, Baker DA, Billker O. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite. PLoS Pathog. 2009 Sep;5(9):e1000599.
Spaccapelo R, Janse CJ, Caterbi S, Franke-Fayard B, Bonilla JA, Syphard LM, Di Cristina M, Dottorini T, Savarino A, Cassone A, Bistoni F, Waters AP, Dame JB, Crisanti A. Plasmepsin 4-deficient Plasmodiumberghei are virulence attenuated and induce protective immunity against experimental malaria. Am J Pathol. 2010;176(1):205-17.
Iwanaga S, Khan SM, Kaneko I, Christodoulou Z, Newbold C, Yuda M, Janse CJ, Waters AP (2010). Functional identification of the Plasmodium centromere and generation of a Plasmodium artificial chromosome. Cell Host Microbe. 7(3):245-55.
Mair GR, Lasonder E, Garver LS, Franke-Fayard BM, Carret CK, Wiegant JC, Dirks RW, Dimopoulos G, Janse CJ, Waters AP. Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog. 2010;6(2):e1000767.
Dijk MR van, BSchaijk BCL van, Khan SM, Dooren MW van, Ramesar J, Kaczanowski S, Gemert GJ van, Kroeze H, Stunnenberg HG, Eling WM, Sauerwein RW, Waters AP, Janse CJ. Three Members of the 6-cys Protein Family of Plasmodium Play a Role in Gamete Fertility. Plos Pathogens. 2010 Apr 8;6(4):e1000853.
Franke-Fayard B, Fonager J, Braks A, Khan SM, Janse CJ. Sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria? PLoS Pathog. 2010; 6(9). pii: e1001032.
Gueirard P, Tavares J, Thiberge S, Bernex F, Ishino T, Milon G, Franke-Fayard B, Janse CJ, Ménard R, Amino R. Development of the malaria parasite in the skin of the mammalian host. Proc Natl Acad Sci U S A. 2010;107(43):18640-5.
Gomes-Santos CS, Braks J, Prudêncio M, Carret C, Gomes AR, Pain A, Feltwell T, Khan S, Waters A, Janse C, Mair GR, Mota MM. Transition of Plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio.PLoS Pathog. 2011; 7(5):e1002046.
Wykes MN, Kay JG, Manderson A, Liu XQ, Brown DL, Richard DJ, Wipasa J, Jiang SH, Jones MK, Janse CJ, Waters AP, Pierce SK, Miller LH, Stow JL, Good MF. Rodent blood-stage Plasmodium survive in dendritic cells that infect naive mice. Proc Natl Acad Sci U S A. 2011 108(27):11205-10.
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. Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo. J Exp Med. 2011 16; 209(1): 93-107.
Annoura T, Ploemen IH, van Schaijk BC, Sajid M, Vos MW, van Gemert GJ, Chevalley-Maurel S, Franke-Fayard BM, Hermsen CC, Gego A, Franetich JF, Mazier D, Hoffman SL, Janse CJ, Sauerwein RW, Khan SM. Assessing the adequacy of attenuation of genetically modified malaria parasite vaccine candidates. Vaccine 2012; 30(16): 2662-70.
Sun T, Holowka T, Song Y, Zierow S, Leng L, Chen Y, Xiong H, Griffith J, Nouraie M, Thuma PE, Lolis E, Janse CJ, Gordeuk VR, Augustijn K, Bucala R. A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria. Proc Natl Acad Sci U S A. 2012; 109(31):E2117-26.
The role of animal models for research on severe malaria. Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, Turner G, Langhorne J; participants of the Hinxton Retreat meeting on Animal Models for Research on Severe Malaria. PLoS Pathog. 2012 Feb;8(2):e1002401
A putative homologue of CDC20/CDH1 in the malaria parasite is essential for male gamete development. Guttery DS, Ferguson DJ, Poulin B, Xu Z, Straschil U, Klop O, Solyakov L, Sandrini SM, Brady D, Nieduszynski CA, Janse CJ, Holder AA, Tobin AB, Tewari R. PLoS Pathog. 2012 Feb;8(2):e1002554.
Genetic engineering of attenuated malaria parasites for vaccination. Khan SM, Janse CJ, Kappe SH, Mikolajczak SA. Curr Opin Biotechnol. 2012 Dec;23(6):908-16.
Proteomic and genetic analyses demonstrate that Plasmodium berghei blood stages export a large and diverse repertoire of proteins. Pasini EM, Braks JA, Fonager J, Klop O, Aime E, Spaccapelo R, Otto TD, Berriman M, Hiss JA, Thomas AW, Mann M, Janse CJ, Kocken CH, Franke-Fayard B. Mol Cell Proteomics. 2013 Feb;12(2):426-48
The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment. Goodman AL, Forbes EK, Williams AR, Douglas AD, de Cassan SC, Bauza K, Biswas S, Dicks MD, Llewellyn D, Moore AC, Janse CJ, Franke-Fayard BM, Gilbert SC, Hill AV, Pleass RJ, Draper SJ. Sci Rep. 2013;3:1706
Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development. Annoura T, van Schaijk BC, Ploemen IH, Sajid M, Lin JW, Vos MW, Dinmohamed AG, Inaoka DK, Rijpma SR, van Gemert GJ, Chevalley-Maurel S, Kielbasa SM, Scheltinga F, Franke-Fayard B, Klop O, Hermsen CC, Kita K, Gego A, Franetich JF, Mazier D, Hoffman SL, Janse CJ, Sauerwein RW, Khan SM. FASEB J. 2014 Feb 7.
van Schaijk BC, Ploemen IH, Annoura T, Vos MW, Foquet L, van Gemert GJ, Chevalley-Maurel S, van de Vegte-Bolmer M, Sajid M, Franetich JF, Lorthiois A, Leroux-Roels G, Meuleman P, Hermsen CC, Mazier D, Hoffman SL, Janse CJ, Khan SM, Sauerwein RW. A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites. Elife. 2014 Nov 19;3.
Guerreiro A, Deligianni E, Santos JM, Silva PA, Louis C, Pain A, Janse CJ, Franke-Fayard B, Carret CK, Siden-Kiamos I, Mair GR. Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte. Genome Biol. 2014 Nov 3;15(11):493.
Burda PC, Roelli MA, Schaffner M, Khan SM, Janse CJ, Heussler VT. A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane. PLoS Pathog. 2015 Mar 18;11(3):e1004760.
Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance. Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, Ravelli RB, Aime E, Capuccini B, Mommaas-Kienhuis AM, O'Toole T, Prins F, Franke-Fayard BM, Ramesar J, Chevalley-Maurel S, Kroeze H, Koster AJ, Tanke HJ, Crisanti A, Langhorne J, Arese P, Van den Steen PE, Janse CJ, Khan SM. J. Exp Med. 2015 212(6):893-903
Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms. Prado M, Eickel N, De Niz M, Heitmann A, Agop-Nersesian C, Wacker R, Schmuckli-Maurer J, Caldelari R, Janse CJ, Khan SM, May J, Meyer CG, Heussler VT. Autophagy. 2015;11(9):1561-79.
Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates. Longley RJ, Salman AM, Cottingham MG, Ewer K, Janse CJ, Khan SM, Spencer AJ, Hill AV. Sci Rep. 2015; 5:11820.
The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites. De Niz M, Ullrich AK, Heiber A, Blancke Soares A, Pick C, Lyck R, Keller D, Kaiser G, Prado M, Flemming S, Del Portillo H, Janse CJ, Heussler V, Spielmann T. Nat Commun. 2016 May 26;7:11659
Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes: molecular insight into sex-specific processes and translational repression. Lasonder E, Rijpma SR, van Schaijk BC, Hoeijmakers WA, Kensche PR, Gresnigt MS, Italiaander A, Vos MW, Woestenenk R, Bousema T, Mair GR, Khan SM, Janse CJ, Bártfai R, Sauerwein RW. Nucleic Acids Res. 2016 Jun 13. pii: gkw536
Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite. Santos JM, Duarte N, Kehrer J, Ramesar J, Avramut MC, Koster AJ, Dessens JT, Frischknecht F, Chevalley-Maurel S, Janse CJ, Franke-Fayard B, Mair GR. Proc Natl Acad Sci U S A. 2016 Jun 14. pii: 201522381
Variant Exported Blood-Stage Proteins Encoded by Plasmodium Multigene Families Are Expressed in Liver Stages Where They Are Exported into the Parasitophorous Vacuole. 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. PLoS Pathog. 2016 Nov 16;12(11):e1005917.
CD8+ T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria via Luminal Antigen-Specific Engagement of Brain Vasculature. Swanson PA 2nd, Hart GT, Russo MV, Nayak D, Yazew T, Peña M, Khan SM, Janse CJ, Pierce SK, McGavern DB. PLoS Pathog. 2016 Dec 1;12(12):e1006022.
1976-1982: Undergraduate/graduate studies at the Faculty of Science (Biology) at the University of Leiden, The Netherlands. Graduate research involved studies on the ecology and host-seeking behaviour of sibling species of parasitic wasps, ecology of bird populations (relationships between species diversity and forest management) and cell-biology of malaria parasites (genetic and environmental factors underlying sexual differentiation).
1983-1986: PhD studies (‘cum laude’) were funded by the Netherlands Organization for Scientific Research and were carried out jointly between the University of Utrecht and the University of Leiden. PhD Studies involved the development of technologies for use on the rodent model of malaria (Plasmodium berghei; in Wikipedia) to investigate sexual differentiation and DNA replication in malaria parasites. For example, technologies for in vitro cultivation of blood stages and sexual stages of the parasite. These technologies have significantly increased the relevance of P. berghei as a model of human malaria and improved the understanding of the developmental biology of malaria parasites at the molecular level, for example insight into the processes of DNA replication during parasite sexual development. Technologies were developed to perform the first separation and characterization of the chromosomes of rodent malaria parasites.
1986-2005: After the PhD, studies in the Department of Parasitology (LUMC, Leiden) focussed on further development of rodent malaria models to investigate the biology of malaria parasites. This research has contributed to the introduction and application of advanced molecular techniques in malaria research such as genomics and post-genomic (transcriptome, proteome) technologies. A major breakthrough was the implementation of technologies that permit genetic modification of rodent malaria parasites; technologies that allowed, for the first time, the generation of malaria parasites that retain stable genetic modifications. These methodologies and others that we developed have opened up new avenues in malarial research and have greatly aided studies on the basic biology of the parasite, studies on host-parasite interaction involved in pathology and contributed to the functional analysis of potential parasite drug and vaccine targets. These studies included genomic- and post-genomic analyses of malaria parasites, contributing to the generation of genome sequences of different malaria parasites and genome wide studies of gene expression (microarrays, RNAseq analyses, proteome analyses).
2005-.... (Head of the Leiden Malaria Group): The current emphasis of the research is on the development of a human malaria vaccine based on genetically attenuated parasites and on the identification and analysis of parasite proteins that are (putative) targets for subunit vaccines.
Leids Universitair Medisch Centrum
2333 ZA Leiden
2300 RC Leiden