About the partners
This project will be represented by DNDi (Scientific Coordination, Farrokh Modabber) and LSHTM (Administrative Management, Simon Croft).
Partner 1: London School of Hygiene & Tropical Medicine (LSHTM)
Tasks: (a) Management: LSHTM is the administrative manager of the project and provides management support and infrastructure for intra-consortium communication. (b) Research: LSHTM will work closely with IICB (4) and HUJI (6) in the development, characterization and validation of in vivo models used in testing the prophylactic and therapeutic vaccines. The experience of LSHTM in working with drugs, drug combinations and immunomodulators in rodent models of infection provides the strong basis for studies on a therapeutic vaccine (WP5) and combinations with adjuvants and chemotherapeutic agents.
Simon L. Croft, PhD, is the Principal Investigator for LSHTM and will coordinate LSHTM activities for the project consortium. Simon Croft draws on over 25 years of experience in the discovery and development of new drugs and formulations for the treatment of leishmaniasis, malaria, human African trypanosomiasis and South American trypanosomiasis. He gained a PhD at the Liverpool School of Tropical Medicine and expertise and experience on anti-parasitic chemotherapy while working with the Wellcome Research Laboratories, Beckenham, UK in the 1980s. His subsequent research while at LSHTM includes projects on miltefosine, AmBisomeTM and topical paromomycin, all of which reached patients for leishmaniasis. Simon Croft was DNDi Research & Development Director between July 2004 and August 2007.
Karin Seifert, PhD, is a Lecturer at LSHTM who joined the School in 2002 for the FP6 MILTLEISH (miltefosine for leishmaniasis) project. Dr Seifert is a pharmacist with experience in drug delivery systems, topical formulations and development of in vitro and in vivo models for leishmaniasis. She undertook the first systematic study of anti-leishmanial drug combinations. Dr. Seifert is the lead scientist of this project and Principal manager at LSHTM.
Selected publications:
1. Seifert, K., Escobar P., Croft S.L. (2010) In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent. Journal of Antimicrobial Chemotherapy, 65, 508-511
2. Nicoletti, S., Seifert, K., Gilbert, I. (2009). N-(2-hydroxypropyl)methacrylamide(HPMA)-amphotericin B conjugates as anti-leishmanial agents. International Journal of Antimicrobial Agents, 33, 441-448
3. Seifert, K. Croft S.L. (2006) In vitro and in vivo interactions between miltefosine and other antileishmanial drugs. Antimicrobial Agents and Chemotherapy, 50, 73-79
4. Perez-Victoria, F.J., Sanchez-Canete, M.P., Seifert, K., Croft, S.L., Sundar, S., Castanys, S., Gamarro, F. (2006). Mechanisms of experimental resistance of Leishmania to miltefosine: implications for clinical use. Drug Resistance update, 9, 26-39
Partner 2: MOLOGEN AG
Tasks: MOLOGEN AG participates in the definition of the vaccine antigens. The MIDGE®-vectors and the candidate vaccine are designed and manufactured by MOLOGEN AG, which is also responsible for the preclinical safety studies. Moreover, the company is involved in the preparation of clinical trials. MOLOGEN AG accompanies the program with management of intellectual property and quality management / assurance.
Matthias Schroff, ScD, is the Chief Executive Officer at MOLOGEN AG. A graduate biochemist, he is specialized in overall DNA vector design and holds great expertise in the field of transfection methods. Matthias Schroff has 17 years of experience in the area of nucleic acid research and is the co-inventor of numerous patented key technologies at MOLOGEN AG. During the past years, he has lead preclinical and clinical studies for DNA based therapeutics for humans.
Christiane Juhls, DVM, is the Head of the DNA Vaccine Department at MOLOGEN AG. She has worked on MIDGE®-based DNA vaccines for ten years and coordinates international vaccine research and development projects. For the past four years, she has been responsible for the canine Leishmaniasis vaccine project at MOLOGEN AG.
Selected publications:
1. Schakowski F, Gorschlüter M, Buttgereit P, Märten A, Lilienfeld-Toal MV, Junghans C, Schroff M, König-Merediz SA, Ziske C, Strehl J, Sauerbruch T, Wittig B, Schmidt-Wolf IG. Minimal size MIDGE vectors improve transgene expression in vivo. In Vivo. 2007 Jan-Feb; 21(1):17-23.
2. Zheng C, Juhls C, Oswald D, Sack F, Westfehling I, Wittig B, Babiuk LA, van Drunen Littel-van den Hurk S. Effect of different nuclear localization sequences on the immune responses induced by a MIDGE vector encoding bovine herpesvirus-1 glycoprotein D. Vaccine. 2006 May 22; 24(21):4625-9.
3. Moreno S, López-Fuertes L, Vila-Coro AJ, Sack F, Smith CA, Konig SA, Wittig B, Schroff M, Juhls C, Junghans C, Timón M. DNA immunisation with minimalistic expression constructs. Vaccine. 2004 Apr 16; 22(13-14):1709-16.
4. Schirmbeck R, König-Merediz SA, Riedl P, Kwissa M, Sack F, Schroff M, Junghans C, Reimann J, Wittig B. Priming of immune responses to hepatitis B surface antigen with minimal DNA expression constructs modified with a nuclear localization signal peptide. J Mol Med. 2001 Jun; 79(5-6):343-50.
5. Schakowski F, Gorschlüter M, Junghans C, Schroff M, Buttgereit P, Ziske C, Schöttker B, König-Merediz SA, Sauerbruch T, Wittig B, Schmidt-Wolf IG. A novel minimal-size vector (MIDGE) improves transgene expression in colon carcinoma cells and avoids transfection of undesired DNA. Mol Ther. 2001 May; 3(5 Pt 1):793-800.
Partner 3: Charité - Universitätsmedizin Berlin (Charite)
Tasks: Charité is mainly involved in the definition of the vaccine antigens (WP1), the characterisation of T cell responses in leishmaniasis patients in acute disease and after cure to identify markers for immunity (WP1), testing the capacity of the vaccine antigens and the complete vaccines to induce human T cell responses (WP3), developing the protocols and establishing SOPs for monitoring vaccine-induced T cell responses during the subsequent vaccination trials and will implement these SOPs at the clinical sites selected for the trials (WP7).
Peter Walden, ScD, is a biochemist specialised in immunology, professor for immuno-dermatology and head of a Clinical Research Group at the Charité Dept. of Dermatology. He has about 30 years experience in T cell immunology and has been for 8 years now working on human leishmaniasis. The above described research programme was initiated and is being directed by him and he will coordinate and supervise the project work at the Charité.
Selected publications:
1. Angana Ghoshal, Sumi Mukhopadhyay, Rodion Demine, Michael Forgber, Saulius Jarmalavicius, Bibhuti Saha, Shyam Sundar, Peter Walden, Chhabinath Mandal and Chitra Mandal (2009). Detection and characterization of a sialoglycosylated bacterial ABC-type phosphate transporter protein from patients with visceral Leishmaniasis. Glycoconjugate Journal 26: 675-89.
2. Rajatava Basu, Suniti Bhaumik, Arun Kumar Haldar, Kshudiram Naskar, Tripti De, Syamal Kumar Dana, Peter Walden and Syamal Roy (2007). Hybrid cell vaccination resolves Leishmania donovani infection by eliciting strong CD8+CTL response with concomitant suppression of IL-10 but not IL-4 and IL-13. Infection and Immunity 75: 5956-5966.
3. Stephan Theinert, Michael Forgber and Peter Walden (2007). Serological immune responses to Leishmania antigens in visceral leishmaniasis. Science and Culture 73: 191-200.
4. Rajatava Basu, Syamal Roy and Peter Walden. (2007). HLA class I-restricted T cell epitopes of the kmp-11 protein presented by Leishmania donovani-infected human macrophages. J. Inf. Diseases. 195: 1373-1380.
5. Michael Forgber, Rajatava Basu, Kaushik Roychoudhury, Stephan Theinert, Syamal Roy, Shyam Sundar and Peter Walden (2006). Mapping the antigenicity of the parasites in Leishmania donovani infection by proteome serology. PLOS One 1 e40: 1-11.
Partner 4: Indian Institute of Chemical Biology (IICB), Kolkata
Tasks: As coordinator of WP3 the main task is to conduct animal experimentation for the prophylactic efficacy of the vaccine. He will also conduct a major part of the works of WP5 for evaluation of the therapeutic efficacy of the vaccines.
Dr. Syamal Roy is heading the immunology group at IICB. His interest centres on macrophage and T cell function in leishmaniasis. He was trained in the Cellular Immunology group in the Department of Biology, Massachusetts Institute of Technology during the late eighties. The main emphasis of his group is to study the cell surface phenomena of parasitised macrophages using fluorescent probes and functional analysis of their antigen presenting function. Dr. Syamal Roy and the research associates and Ph.D. students in the laboratory are involved in Leishmania research and will support the work on the project proposed herewith.
Selected publications:
1. Banerjee Subha, Ghosh June, Sen Subha, Guha Rajan, Dhar Ranjan, Ghosh Moumita, Datta Sanchita, Raychaudhury Bikramjit, Naskar Kshudiram, Haldar Aarun Kumar, Lal CS, Pandey K, Das VN, Das Pradeep, Roy Syamal (2009). Designing therapies against experimental visceral leishmaniasis by modulating the membrane fluidity of antigen-presenting cells. Infection Immunity 77: 2330-2342
2. Bhaumik Suniti, Basu Rajatava, Sen Subha, Naskar Kshudiram, Roy Syamal (2009). KMP-11 DNA immunization significantly protects against L. donovani infection but requires exogenous IL-12 as an adjuvant for comparable protection against L. major. Vaccine 27: 1306-1316
3. Basu Rajatava, Bhaumik Suniti, Haldar Aarun Kumar, Naskar Kshudiram, De Tripti, Dana Syamal Kumar, Walden Peter, Roy Syamal (2007). Hybrid cell vaccination resolves Leishmania donovani infection by eliciting a strong CD8+ cytotoxic T-lymphocyte response with concomitant suppression of interleukin-10 (IL-10) but not IL-4 or IL-13. Infection and Immunity 75: 5956-5966
4. Basu Rajatava, Roy Syamal, Walden Peter (2007). HLA class I-restricted T cell epitopes of the kinetoplastid membrane protein-11 presented by Leishmania donovani-infected human macrophages. Journal of Infectious Diseases 195:1373-1380
5. Basu Rajatava, Bhaumik Suniti, Basu Jayati Mookerjee, Naskar Kshudiram, De Tripti, Roy Syamal (2005). Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: evidence for mixed Th1- and Th2-like responses in visceral leishmaniasis. The Journal of Immunology 174:7160-7171.
Partner 5: Institut Pasteur de Tunis (IPT)
Tasks: In addition to its involvement in the different steps of the proposal, IPT will be mainly involved in the definition of the vaccine antigens (WP-1), more specifically IPT will contribute for the determination of the T cell-stimulatory capacity of the selected vaccine antigens. IPT could also constitute one of the sites for conducting clinical trials of LEISHDNAVAX (WP-7).
Hechmi Louzir, MD, is the General Director of IPT and the head of the LIVGM. He will coordinate IPT activities for the project consortium. Hechmi Louzir draws on over 15 years of experience in laboratory and field studies of the different forms of human leishmaniasis prevalent in Tunisia (L. major, L. infantum and L. tropica). He is involved in several projects aiming at the identification of new tools (diagnostics and vaccines) for the control of leishmaniasis.
Mehdi CHENIK, PhD; has a strong experience in the molecular biology of Leishmania parasite, and a good experience in the cellular immunology of cutaneous Leishmaniasis. He described some potentially secreted/excreted parasite antigens that could constitute a candidate vaccine.
Amel Garnaoui, PhD., will contribute to the analysis of the cellular immune response of individuals exposed to Leishmania infection.
Thouraya Bousoffara, PhD, Postdoctoral Fellow at IPT, LIVGM, was involved in research studies aiming to the characterization of human immune correlates for protection against leishmaniasis. In the present project, she will be in charge of the evaluation of the immunogenicity of the candidate antigens.
Ikbel Naouar, PhD student will be particularly involved in the analysis of the cytotoxic T cell response, including FACS analysis for concomitant analysis of the phenotype of activated T cells and the intracellular cytokine.
Selected publications:
1. Meddeb-Garnaoui A, Toumi A, Ghelis H, Mahjoub M, Louzir H, Chenik M. Cellular and humoral responses induced by Leishmania histone H2B and its divergent and conserved parts in cutaneous and visceral leishmaniasis patients, respectively. Vaccine. 2009 Dec 14. PMID: 20005858.
2. Lakhal-Naouar I, Boussoffara T, Meddeb-Garnaoui A, Ben Achour-Chenik Y, Louzir H, Chenik M. Cellular and humoral responses to Leishmania major virulence factors in healed cutaneous leishmaniasis and Mediterranean visceral leishmaniasis patients. Clin Vaccine Immunol. 2009 Jun;16(6):956-8
3. Gradoni L, Soteriadou K, Louzir H, Dakkak A, Toz S.O., Jaffe Ch, Dedet J.P., Campino L, Canavate C, Dujardin J.C. Drug regimens for visceral leishmaniasis in Mediterranean countries. Trop. Med. Int. Health. 2008, 13(10):1272-6.
4. Lakhal-Naouar I, Achour-Chenik YB, Boublik Y, Meddeb M, Aamouri A, Fattoum A, Louzir H, Chenik M. Identification and characterization of a new Leishmania major specific 3'nucleotidase/nuclease protein. Biochem Biophys Res Commun. 2008 Oct 10;375(1):54-8.
5. Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. Lancet Infect Dis. 2007;7(9):581-96.
Partner 6: Hebrew
University of Jerusalem (HUJI)
Tasks: Research: HUJI will work closely with LSHTM (1) and IICB (4) on the testing and immunological evaluation of prophylactic and therapeutic vaccines in hamster models. In addition, we will be involved in studies on the degree of sequence conservation of vaccine antigens in recent Leishmania isolates from patients, and expression and purification of recombinant antigens in cooperation with MAG (2) and IICB (4).
Dr. Charles L. Jaffe is the head of the Department of Parasitology and a member of the Kuvin Centre. His research has focused on the development of diagnostic assays, studies on immunology of leishmaniasis and role of protein kinases in parasite survival. He has collaborated extensively on leishmaniasis research with colleagues from North Africa, the Middle East, India, South America, the United States and Europe, and organized training workshops in India, Morocco and Uzbekistan.
Selected publications:
1. Talmi-Frank, D., Nasereddin, A., Schnur, L.F., Schönian, G., Özensoy Töz, S., Jaffe, C.L. and Baneth, G. (2010). Detection and Identification of Old World Leishmania by High Resolution Melt Analysis. PLoS NTD, In press.
2. Malki-Feldman, L. and Jaffe, C.L. (2009). Leishmania major: Effect of Protein kinase A and Phosphodiesterase activity on infectivity and proliferation of promastigotes. Exp. Parasitol. 123, 39-44
3. Nasereddin, A., Bensoussan-Hermano, E., Schönian, G., Baneth, G. and Jaffe, C.L. (2008). Molecular Diagnosis and Species Identification of Old Word Cutaneous Leishmaniasis using a Reverse Line Blot Hybridization Assay. J Clin Microbiol. 46, 2848-2855.
4. Strauss-Ayali, D., Baneth, G. and Jaffe, C.L. (2007) Splenic immune responses during canine visceral leishmaniasis. Vet Parasitol 38, 547-564.
Partner 7: Rajendra Memorial Research Institute of Medical Sciences (RMRI)
Tasks: To identify sites for carrying out clinical trials. Preparation and training for monitoring the trials of LEISHDNAVAX (WP7). To carry out the immunological studies on animals with IICB (WP3). To participate in immunological studies on human cells (WP1).
Dr. Pradeep Das is the Director of RMRI and has worked for last two decades in the field of intestinal and blood parasites. Presently, he is the PI of 11 externally granted national and international projects. His group mainly works on differential gene expression in two forms of Leishmania, innate immune response, drug resistance mechanism, cell death, apoptosis, cell signalling and proteomics in Leishmania patients. His field of specialization is molecular immunology. He has his expertise in raising monoclonal antibody, ELIZA, cDNA library generation and microarray technology.
Selected publications:
1. S. Banerjee, J. Ghosh, S. Sen, R. Guha, R. Dhar, M. Ghosh, S. Datta, B. Raychaudhury, K. Naskar, AK. Haldar, CS. Lal, K. Pandey, VNR Das, P. Das, S. Roy. Designing therapies against experimental visceral leishmaniasis by modulating the membrane fluidity of antigen presenting cells. Infect Immun. 2009 Mar 16. [Epub ahead of print]
2. S. Narayan, S. Bimal, SK. Singh, AK. Gupta, VP. Singh, PK Sinha and P. Das. Leishmania donovani vs immunity: T-cells sensitized from Leishmania of one donor may modulate their cytokines pattern on re-stimulation with Leishmania from different donor in visceral leishmaniasis. Exp Parasitol. 121(1):69-75. (2009)
3. D. Mondal, S.P. Singh, N. Kumar, A. Joshi, S. Sundar, P. Das, H. Siddhivinayak, A. Kroeger and M. Boelaert. Visceral leishmaniasis elimination programme in India, Bangladesh, and Nepal: reshaping the case finding/case management strategy. PLoS Negl Trop Dis.;3(1):e355 (2009)
4. V.N.R. Das, K. Pandey, N. Verma, C.S. Lal, S. Bimal, R.K.Topno, D. Singh, N.A. Siddiqui, R. Verma and P. Das. Short report: Development of post-kala-azar dermal leishmaniasis (PKDL) in miltefosine-treated visceral leishmaniasis.American Journal of Tropical medicine and Hygiene. Mar;80(3):336-8. (2009)
Partner 8: Drugs for Neglected Diseases Initiative (DNDi)
Tasks: (a) Scientific Coordination: DNDi will be the scientific co-ordinator of the project and work closely with all partners on selection of candidates, preclinical development, interactions with regulatory authorities to assure meeting the requirements for clinical studies and scientific communications. (b) Identification of sites and training as well as infrastructure building toward conducting clinical trials at ICH-GCP levels. (c) Scientific representation of the project in collaboration with other partners.
Farrokh Modabber, Ph.D. is the Scientific Coordinator of the project, who conceptualized, formulated and brought Partners together to develop LEISHDANVAX project. He received a Bachelor's degree in Bacteriology and a Ph. D. in Microbiology (Immunology) from UCLA and was a Harvard Fellow at Harvard Medical School before joining the faculty at Harvard School of Public Health as Assistant Professor. He is Senior Project Manager at DNDi. Farrokh has extensive experience in: Academia; Research Institutes: (Professor & Director General, Pasteur Institute, Iran; Director, Infectious Disease Research Inst., Seattle, USA; Visiting Scientist at Institut Pasteur, Paris); Industry: (Syntex, now Roche, Choay, Bayer, Mologen); and International Organizations: (Tropical Disease Research TDR/WHO). His major interest is prophylaxis and treatment of leishmaniases. He initiated leishmaniasis vaccine program at TDR and participated in most of the first generation vaccine trials. He directed the initial clinical development phases of LEISH-111f + MPL-SE, the first defined vaccine against leishmaniasis in the U.S. He has worked in the field with scientists in Brazil, Colombia, Ecuador, Ethiopia, Guatemala, India, Iran, Kenya, and Sudan. He is an honorary professor at LSHTM.
Shing Chang, Ph.D. Director of Research and Development at DNDi, has the overall responsibility of building DNDi's project portfolio and advancing the discovery and development of new treatments for neglected diseases. Prior to joining DNDi in October 2007, Dr. Chang held various executive positions in pharmaceutical industry. He served as Senior Vice President, Drug Discovery and Chief Scientific Officer at ICOS Corporation; held various management positions at Abbott Laboratories in diagnostics and pharmaceutical research, including seven years as Divisional Vice President, Infectious Disease Research, in the global pharmaceutical research and development division; and was Vice President, Preclinical and Development at Cetus Corporation after joining initially as one of its first molecular biologists. Dr Chan brings a wealth of experience in development of therapeutics. As the Director of R&D, Dr Chan will follow our activities and provide advice for efficient development of LEISHDNAVAX. Dr. Chang received a BS in Biology from Fu-Jen Catholic University in Taiwan, PhD in Molecular Biology and Biochemistry from the University of California, Santa Barbara, and completed postdoctoral fellowships at the University of Wisconsin and Stanford University.
Bhawna Sharma, PhD, Head of Regional Support Office, DNDi India. Dr. Sharma joined DNDi as a consultant in December 2004 and is currently the Head of the Regional Support Office in DNDi India. In her role, she coordinates clinical research projects and facilitates partner relations in India. Most recently, Dr. Sharma served as a research scientist with the Indian Council of Medical Research, where she gained research and regulatory affairs experience. She also previously taught pharmacology at the All India Institute of Medical Sciences (A.I.I.M.S.) in New Delhi and served as an editor for the JAMA India Medical journal. During her post graduate work, she was involved in pharmacokinetic and cardiovascular studies. Bhawna will bring her expertise in regulatory requirements for preclinical and clinical development in India, a part of our plan of activity in LEISHDNAVAX. Dr Sharma received her PhD and completed post-doctoral fellowships in pharmacology and drug assay at A.I.I.M.S.
Sally Ellis (Hon B.SC.), Clinical Project Coordinator, Senior Clinical Research Associate, DNDi. She coordinates several clinical trials of drug combination treatments in East Africa and India and is setting up and will manage a new drug combination trial in Bangladesh. Ms Ellis most recently served as a global study manager/ study management team leader at F. Hoffman-la Roche in Basel, Switzerland. She has extensive experience in clinical research, has conducted numerous workshops on ICH-GCP in which she is an expert having held various positions with ICON Clinical Research, Innovata Biomed Ltd, and SmithKline Beecham. Ms. Ellis completed an honours bachelor's of science (Hons. B.Sc.) degree in Immunology at King's College in London.
Selected publications:
1. Musa AM, Noazin S, Khalil EAG, Modabber F. Immunological stimulation for treatment of leishmaniases: A modality worthy of serious consideration. Trans. Roy. Soc. Trop. Med. Hyg. (mini-review), 2010; 104:1-2
2. Modabber F, Coler R & Reed S. Vaccines against Leishmania. In New Generation Vaccines. Levine M et al. Eds. 4th Edition. Informa USA publishers, Chapter 82, 2009
3. Musa AM, Khalil EAG, Mahgoub FAE, Elgawi SHH, Modabber F, Elkadaru AEMY, et.al. Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach of treatment. Trans Roy Soc. Trop. Med. 2008, 102:58-63.
4. Noazin S, Modabber F, Khamesipour A, Smith PG, Moultone LH, Nasseri Q, Sharifi I, Khalil EAG, Velez ID, Antunes CA, Kieny MP & Tanner M. First generation leishmaniasis vaccines: A review of field efficacy trials. Vaccine, 2008, 26:6759-67
5. Noazin S, Khamesipour A, Moulton LH, Tanner M, Nasseri K, Modabber F, et al. Efficacy of killed whole-parasite vaccines in the prevention of leishmaniasis-A meta-analysis. Vaccine, 2009; 27:4747-53.