Experimental infection and protection against ... - TI Pharma

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Chapter 8 Induction of malaria in volunteers by intradermal injection of cryopreserved Plasmodium falciparum sporozoites Meta Roestenberg a,1 , Else M. Bijker a,1 , B. Kim Lee Sim b,c , Peter F. Billingsley b , Eric R. James b , Guido J.H. Bastiaens a , Anne C. Teirlinck a , Dunja Zimmerman a , Karina Teelen a , Theo Arens a , Pieter Beckers a , Annemieke Jansens a , Anja Scholzen a , Adrian J.F. Luty a,* , Krystelle Nganou-Makamdop a , Jorien Wiersma a , André J.A.M. van der Ven d , Anusha Gunasekera b , Adam Richman b , Sumana Chakravarty b , Soundarapandian Velmurugan b , Tao Li b , Anita Manoj b , Abraham G. Eappen b , Minglin Li c , Richard E. Stafford b,c , Cornelus C. Hermsen a , Robert W. Sauerwein a,2 , Stephen L. Hoffman b,2 1 contributed equally to this study 2 contributed equally to this study a Radboud University Nijmegen Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands b Sanaria Inc., Rockville, USA c Protein Potential LLC, Rockville, USA d Radboud University Nijmegen Medical Center, Department of General Internal Medicine, Nijmegen, The Netherlands * Current address: Institut de Recherche pour le Développement, UMR 216 Mère et enfant face aux infections tropicales, Paris, France/Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, France. Am. J. Trop. Med. Hyg. 2012; nov.13
152 Chapter 8 Abstract Vaccines and new drugs are needed to prevent the approximately one million deaths and hundreds of millions of cases caused by Plasmodium falciparum (Pf) malaria annually. To test these vaccines and drugs, volunteers are infected by the bites of Pf sporozoite (SPZ)-infected mosquitoes under controlled conditions. Such infections are limited to the few centres with production of PfSPZ-infected mosquitoes. We assessed the capacity to infect volunteers by intradermal (ID) injection of aseptic, purified, vialed, cryopreserved PfSPZ (PfSPZ Challenge). Dutch volunteers received ID injections of PfSPZ that had been cryopreserved for 27-30 months. In a dose escalation study volunteers (N=6/group) received 2,500, 10,000, or 25,000 PfSPZ. Detection of blood-stage parasites by microscopy was the primary outcome. Kinetics of parasitemia were retrospectively assessed by quantitative PCR. Fifteen of eighteen volunteers (84%) developed Pf parasitemia, 5/6 volunteers at each dose. Infection was safe. There were no differences between groups in time until parasitemia by microscopy and PCR, parasite kinetics, clinical symptoms and signs or laboratory values. Aseptic, purified, vialed, cryopreserved PfSPZ manufactured in compliance with regulatory standards and administered ID successfully infected volunteers. Following optimization of administration, such PfSPZ could be used to assess efficacy of vaccines and drugs in clinical trial centres worldwide. In addition PfSPZ Challenge can also be used for immunization strategies against malaria. For example, 100% protection against Pf infection in volunteers immunized by exposure to PfSPZ-infected mosquitoes while taking chloroquine was recently demonstrated. PfSPZ Challenge could be used to translate this artificial immunization protocol into an implementable vaccine.
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Experimental infection and protecti
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Experimental infection and protecti
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Contents Contents 5 Chapter 1 - Int
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Introduction 9 Malaria Malaria is o
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Introduction 11 Preclinical Clinica
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Introduction 13 pipeline of clinica
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Introduction 15 The division of ant
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Introduction 17 Figure 4. Populatio
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Introduction 19 candidates. Initial
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Introduction 21 - to identify param
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Introduction 23 20. Nussenzweig RS,
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Introduction 25 50. Ouedraogo AL, R
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Introduction 27 RTS,S/AS02 in malar
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Chapter 2 Safety and Immunogenicity
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Safety and Immunogenicity of a Reco
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Chapter 3 Humoral immune responses
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Humoral immune responses to a singl
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Chapter 4 82 Abstract The functiona
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84 Chapter 4 Figure 1. Schematic re
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86 Chapter 4 Concentration (mg/ml,
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88 Chapter 4 Figure 4: Correlation
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90 Chapter 4 positively correlated
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92 Chapter 4 Acknowledgements The a
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94 Chapter 4 determinant of subsequ
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Chapter 5 Comparison of clinical an
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Comparison of clinical and parasito
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202 Chapter 10 Figure 3. Mean numbe
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204 Chapter 10 Figure 4. Number of
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206 Chapter 10 temperature (Pearson
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208 Chapter 10 immune modulating ef
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210 Chapter 10 cytokine measurement
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212 Chapter 10 14. Hermsen CC, Telg
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Chapter 11 General Discussion
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General Discussion 217 occurrence o
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General Discussion 219 mediating th
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General Discussion 221 AMA1 express
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General Discussion 223 troponins ca
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General Discussion 225 and between
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General Discussion 227 immunologica
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General Discussion 229 to induce pr
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General Discussion 231 Conclusions
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General Discussion 233 References 1
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General Discussion 235 polymorphonu
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General Discussion 237 57. Church L
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General Discussion 239 85. Beier JC
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General Discussion 241 118. Mueller
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Chapter 12 Summary Samenvatting Lis
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246 Chapter 12 Controlled human mal
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Summary, Samenvatting, List of publ
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254 Chapter 12 Roestenberg M, Teirl
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