Experimental infection and protection against ... - TI Pharma

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Chapter 3 Humoral immune responses to a single allele PfAMA1 vaccine in healthy malarianaïve adults. Edmond J. Remarque* 1 , Meta Roestenberg 2 , Sumera Younis 1 , Vanessa Walraven 1 , Nicole van der Werff 1 , Bart W. Faber 1 , Odile Leroy 3 , Robert Sauerwein 2 , Clemens H.M. Kocken 1 Alan W. Thomas 1 Biomedical Primate Research Centre, Rijswijk, The Netherlands Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands European Vaccine Initiative, Heidelberg, Germany PLoS ONE, 2012;7(6):e38898.
Chapter 3 58 Abstract Plasmodium falciparum apical membrane antigen 1 (AMA1) is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 µg) of a single allele AMA1 antigen formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naïve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i) antibody responses to various allelic variants, (ii) domain specificity, (iii) avidity, (iv) IgG subclass levels, by ELISA and (v) functionality of antibody responses by Growth Inhibition Assay. About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay (GIA) activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains.
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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
Page 10 and 11: Introduction 9 Malaria Malaria is o
Page 12 and 13: Introduction 11 Preclinical Clinica
Page 14 and 15: Introduction 13 pipeline of clinica
Page 16 and 17: Introduction 15 The division of ant
Page 18 and 19: Introduction 17 Figure 4. Populatio
Page 20 and 21: Introduction 19 candidates. Initial
Page 22 and 23: Introduction 21 - to identify param
Page 24 and 25: Introduction 23 20. Nussenzweig RS,
Page 26 and 27: Introduction 25 50. Ouedraogo AL, R
Page 28: Introduction 27 RTS,S/AS02 in malar
Page 32 and 33: Chapter 2 Safety and Immunogenicity
Page 34 and 35: Safety and Immunogenicity of a Reco
Page 60 and 61: Humoral immune responses to a singl
Page 80: Humoral immune responses to a singl
Page 83 and 84: Chapter 4 82 Abstract The functiona
Page 85 and 86: 84 Chapter 4 Figure 1. Schematic re
Page 87 and 88: 86 Chapter 4 Concentration (mg/ml,
Page 89 and 90: 88 Chapter 4 Figure 4: Correlation
Page 91 and 92: 90 Chapter 4 positively correlated
Page 93 and 94: 92 Chapter 4 Acknowledgements The a
Page 95 and 96: 94 Chapter 4 determinant of subsequ
Page 98 and 99: Chapter 5 Comparison of clinical an
Page 100 and 101: Comparison of clinical and parasito
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Comparison of clinical and parasito
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Chapter 6 Efficacy of pre-erythrocy
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Efficacy of pre-erythrocytic and bl
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Chapter 7 NF135.C10: a new Plasmodi
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NF135.C10: a new Plasmodium falcipa
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Chapter 8 Induction of malaria in v
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Induction of malaria in volunteers
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Section 3 Whole parasite inoculatio
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174 Chapter 9 Abstract An effective
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176 Chapter 9 Figure 1. Study desig
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178 Chapter 9 followed by five iden
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180 Chapter 9 Figure 2. Parasitemia
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182 Chapter 9 Test Day I-1 Day C-1
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184 Chapter 9 strain P. falciparum-
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186 Chapter 9 protective role in ot
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188 Chapter 9 References 1. Greenwo
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190 Chapter 9 27. Orjih AU. Acute m
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192 Chapter 9 medium A (Caltag Labo
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194 Chapter 10 Abstract Induction o
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196 Chapter 10 Pre-erythrocytic sta
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198 Chapter 10 procedures described
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200 Chapter 10 by hand-dissection.
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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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