Experimental infection and protection against ... - TI Pharma

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Chapter 4 A saturation of antibody avidity and concentration induced by malaria vaccine candidate Apical Membrane Antigen 1 Meta Roestenberg 1 , Ed Remarque 2 , Bart Faber 2 , Clemens Kocken 2 , Alan Thomas 2 , Cornelus C. Hermsen 1 , Will Roeffen 1 , Robert W. Sauerwein 1 1 Radboud University Nijmegen Medical Centre, department of Medical Microbiology 268, P.O Box 9101, 6500 HB, Nijmegen, The Netherlands 2 Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands Manuscript in preparation
Chapter 4 82 Abstract The functional activity of antibodies is determined by their quantity and quality. Antibody avidity describes the quality of antigen-antibody binding, but this parameter has received only limited attention in vaccine design. The asexual erythrocytic stage antigen Apical Membrane Antigen 1 (AMA1) is a potential Plasmodium falciparum vaccine candidate because of its critical role in red blood cell invasion. AMA1 induces antibody-mediated protection against infection in animals by blocking invasion of the parasite. Assuming a simple 1:1 interaction model of immunoglobulin with antigen, we determined anti-AMA1 antibody concentration and avidity in rabbit and human sera post-vaccination by Surface Plasmon Resonance (SPR) technology. We show that anti-AMA1 antibody concentration and avidity are inversely correlated and become saturated at a maximum fraction of bound antigen. The matured AMA1 antibody response, whether induced through vaccination or natural exposure, thus always has a maximum saturated, constant capacity to bind AMA1 antigen, although there is some interindividual variation in the balance between concentration and avidity. The functionality of these antibodies in vitro was tested by the parasite growth inhibition assay. Growth inhibition in vitro correlated with antibody concentration, but not with avidity. The relevance of these findings in vivo warrants further research, as the appreciation of a saturated antibody response may guide AMA1 vaccine development.
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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
Page 32 and 33: Chapter 2 Safety and Immunogenicity
Page 34 and 35: Safety and Immunogenicity of a Reco
Page 58 and 59: Chapter 3 Humoral immune responses
Page 60 and 61: Humoral immune responses to a singl
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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
Page 118 and 119: Chapter 6 Efficacy of pre-erythrocy
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Page 130 and 131: 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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