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Abstract
The ability to culture pathogenic organisms substantially enhances the quest for fundamental knowledge and the development of vaccines and drugs. Thus, the elaboration of a protocol for the in vitro cultivation of the erythrocytic stages of Plasmodium falciparum revolutionized research on this important parasite. However, for P. vivax, the most widely distributed and difficult to treat malaria parasite, a strict preference for reticulocytes thwarts efforts to maintain it in vitro. Cultivation of P. cynomolgi, a macaque-infecting species phylogenetically close to P. vivax, was briefly reported in the early 1980s, but not pursued further. Here, we define the conditions under which P. cynomolgi can be adapted to long term in vitro culture to yield parasites that share many of the morphological and phenotypic features of P. vivax. We further validate the potential of this culture system for high-throughput screening to prime and accelerate anti-P. vivax drug discovery efforts.
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1 Singapore Immunology Network, A*STAR, Singapore, Singapore; Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; Novartis Institute for Tropical Diseases, Singapore, Singapore
2 Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; Novartis Institute for Tropical Diseases, Singapore, Singapore
3 Singapore Immunology Network, A*STAR, Singapore, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
4 Singapore Immunology Network, A*STAR, Singapore, Singapore; Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
5 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand
6 Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands
7 Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, USA
8 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
9 Novartis Institute for Tropical Diseases, Singapore, Singapore
10 Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University, Atlanta, USA; Emory Vaccine Center, Emory University, Atlanta, USA
11 Laboratory Animal Services, Scientific Operations, Novartis Institutes for Biomedical Research, East Hanover, USA
12 Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford Old Road Campus, Oxford, UK
13 Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; CIMI-Paris, INSERM, U1135, CNRS, Paris, France
14 Emory Vaccine Center, Emory University, Atlanta, USA; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, USA
15 CEA-Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT Department, Fontenay-aux-Roses, France
16 Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; CIMI-Paris, INSERM, U1135, CNRS, Paris, France; CEA-Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT Department, Fontenay-aux-Roses, France
17 Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
18 Singapore Immunology Network, A*STAR, Singapore, Singapore; Novartis Institute for Tropical Diseases, Singapore, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK