Malaria Immunology (Chemical Immunology and Allergy, Vol. 80)

Despite extensive efforts to control it, malaria is still one of the most devastating infectious diseases worldwide. This book, now in its second edition, provides a broad and up-to-date overview of the rapidly expanding field of malaria immunology and its importance in the control of this disease. The first section deals with the malaria parasite and its interactions with both the vertebrate host and the mosquitoes which transmit the disease. In the second part, the mechanisms of immunity and their regulation by environmental and genetic factors are discussed. Finally, this volume contains several chapters on malaria vaccine development, describing the application of the most recent vaccine technologies as well as ongoing and planned vaccine trials. Authored by well-recognized experts, this volume not only demonstrates the rapid progress being made in the search for vaccines against malaria, but also broadens our understanding of immunity to infection in general. It is therefore highly recommended reading for all scientists and professionals in the fields of immunology, infection and vaccine development. Contents......Page 6 Preface......Page 16 Life Cycle......Page 18 Host Cell Entry......Page 21 Trophozoites and Schizonts......Page 24 Knob Formation and Cytoadherence......Page 25 Cytoplasmic Clefts......Page 27 Sexual Forms......Page 28 Fertilization and Zygote Formation......Page 30 Ookinete and Oocyst......Page 31 Sporozoite......Page 33 Preerythrocytic Schizogony......Page 34 Acknowledgements......Page 36 References......Page 37 Introduction......Page 44 Gametocytes......Page 45 Zygote-Ookinete Differentiation......Page 47 Biology of Oocyst Differentiation......Page 49 Biology of Sporozoite Development......Page 51 Insect Innate Immunity......Page 52 Melanisation and Encapsulation of Malaria Parasites......Page 53 Spatio-Temporal Immune Responses to Malaria Infection......Page 55 Serine Proteases and Serpins......Page 56 Transcriptional Control of Immune Responses......Page 57 Parasite Development in the Mosquito as a Target for Malaria Control......Page 58 Engineering Parasite Refractory Mosquitoes......Page 59 References......Page 60 Epidemiology of Disease......Page 67 Reactive Oxygen Species......Page 68 Cytokines......Page 69 Nitric Oxide......Page 71 Mild Malaria......Page 72 Severe Malarial Anaemia......Page 73 Respiratory Distress......Page 75 Disturbances of Consciousness and CM......Page 76 Brain Swelling......Page 77 Renal Disease......Page 78 Shock, Cardiovascular and Pulmonary Disease......Page 79 Disease in Pregnancy......Page 80 References......Page 81 Introduction......Page 87 CS Protein......Page 88 Thrombospondin-Related Anonymous Protein......Page 90 Sporozoite Development in the Mosquito......Page 91 Sporozoite Invasion of Salivary Glands......Page 92 Development of Infectivity by Sporozoites......Page 93 Sporozoite Invasion of Hepatocytes......Page 94 Experimental and Naturally Acquired Immunity to Sporozoites......Page 97 Immune Effector Mechanisms......Page 98 T and B Cell Epitopes of CS Proteins......Page 100 Synthetic Peptide Vaccines Based on the CS Protein......Page 102 Targeting the Intracellular Parasite......Page 106 Conclusions......Page 107 References......Page 108 Introduction......Page 114 Biology of Liver-Stage Malaria Parasites......Page 115 Liver-Stage Antigen-1......Page 116 Liver-Stage Antigen-3......Page 117 CSP-2......Page 118 Mechanisms of Protective Immunity to Liver-Stage Parasites......Page 119 LSA-1......Page 124 GLURP......Page 126 HLA and Genetic Resistance to Liver-Stage Antigens......Page 127 Adjuvants and Delivery Systems......Page 128 Granulocyte-Macrophage Colony-Stimulating Factor......Page 129 LSA-1......Page 130 Ty and VLP Articulate Delivery Systems: The Importance of Prime-Boost Strategies......Page 131 Ty Particle Prime, Vaccinia Virus Boost......Page 132 References......Page 133 Merozoite Antigens Involved in Invasion......Page 142 Erythrocyte Receptors......Page 143 Integral Membrane Proteins......Page 145 Merozoite Surface-Associated Antigens......Page 149 Antigens of Micronemes......Page 151 Rhoptry Antigens......Page 152 Antigens of Dense Granules......Page 153 Acknowledgements......Page 154 References......Page 155 Asexual Blood Stages of Malaria Antigens: Cytoadherence......Page 161 Host Adhesion Receptors......Page 162 Adhesion and Pathogenesis......Page 164 Var Genes and the P. falciparum Adhesion Receptor, PfEMP1......Page 166 Adhesion Domains in PfEMP1......Page 168 CIDR1-α: A Multi-Adhesive Domain that Binds to CD36......Page 169 DBL-γ and Adhesion to CSA......Page 170 Modulation of Parasite Adhesion......Page 171 Adhesion of PEs under Flow......Page 172 References......Page 174 Rosetting......Page 180 Prevalence of Rosetting and Autoagglutinating Malaria Parasites......Page 182 Association of Rosetting and Autoagglutination with Severe Disease......Page 186 The Molecular Basis of Rosetting: Multiple Host Receptors......Page 187 Several Serum Proteins......Page 191 One Parasite Ligand Family......Page 192 Autoagglutination Mechanisms......Page 195 Rosetting, Autoagglutination, Multiadhesion, and Severe Malaria......Page 196 References......Page 198 Introduction......Page 205 Antigens Expressed on Surface Membrane of Red Blood Cells with Gametocytes......Page 206 Pfs16......Page 207 Pfg27......Page 208 Pfs48/45......Page 209 Pfs230......Page 211 Pfs25 and Pfs28......Page 212 Circumsporozoite and TRAP-Related Protein......Page 214 Conclusions......Page 215 References......Page 216 Introduction......Page 221 Mechanisms of Protective Immunity to Blood-Stage Infections......Page 222 Activation of T Cells in a Malaria Infection in Mice......Page 224 Heterogeneity of CD4 T Cells in Malaria......Page 227 Regulation of the Immune Response......Page 231 Pathology of Mouse Malaria Infections......Page 232 Cerebral Malaria......Page 233 Anemia in Malaria Infection......Page 235 Hypoglycemia in Malaria......Page 236 References......Page 238 Innate Immunity......Page 246 Some Important Malaria Antigens......Page 248 Antibody-Dependent Protection......Page 249 CD4+ and CD8+ T Cells......Page 250 γδ T Cells......Page 251 Nitric Oxide......Page 252 Malaria and Pregnancy......Page 253 References......Page 254 Genomics of the P. falciparum Parasite......Page 260 Host Genetic Contributions to Malaria Susceptibility......Page 261 Red Blood Cell Polymorphisms......Page 262 Linkage of MHC (and Non-MHC) Genes with Immunity and Pathogenesis in Malaria......Page 263 Other Genes Associated with Immune Responsiveness......Page 264 References......Page 265 Design Considerations for a Malaria Vaccine......Page 270 The Circumsporozoite Protein as the Basis of a Malaria Vaccine......Page 271 Initial Development of Candidate Malaria Vaccine ‘RTS,S’......Page 272 Initial Field Trials of Candidate Malaria Vaccine ‘RTS,S’......Page 273 Platform Technologies for a Multicomponent, Multistage Vaccine......Page 275 References......Page 276 Introduction......Page 279 Attacking Parasites Developing within Erythrocytes......Page 282 Blocking/Reversing Cytoadherence......Page 283 Candidate Antigens for Vaccine Development......Page 284 MSP1......Page 285 MSP3......Page 286 AMA1......Page 287 SERA......Page 288 RAP1 and RAP2......Page 289 PfEMP1......Page 290 Recombinant Protein and Synthetic Peptide Based-Vaccines......Page 291 DNA Vaccines......Page 292 Prime-Boost Strategy for Optimization of Vaccine-Induced Immune Responses......Page 293 Future Direction: Antigen Discovery through Genomics Research......Page 294 Acknowledgements......Page 295 References......Page 296 The Goals of Attacking Sexual-Stage Parasites with Transmission-Blocking Vaccines......Page 304 The Path Leading to and the Biological Basis for Transmission-Blocking Vaccine Development......Page 305 Late Gametocytes......Page 306 Invasion of the Mosquito......Page 307 Mechanisms of Transmission-Blocking Immunity and Immune Evasion: The Basis for Clinical Assays in Support of Vaccine Development......Page 308 Immune Response to Pre-Fertilization Target Antigens – The Basis for in vitro Surrogate Assays of Vaccine Efficacy......Page 309 Complement-Mediated Lysis......Page 310 Antigenic Diversity – The Need for Polyvalent Transmission-Blocking Vaccines......Page 311 Boosting after a Natural Infection......Page 312 Immune Responses to Post-Fertilization Target Antigens – The Basis for Early Clinical Field Trials......Page 313 Immunogen Production......Page 314 Safety Studies and Interpretation of Early Phase-I Immunogenicity Data......Page 316 Initial Proof of Concept: Phase-IIb Studies......Page 317 Analytical and Clinical Validation of Clinical Surrogate Assays......Page 318 Paths Forward......Page 319 Vaccine Formulations......Page 320 Roadblocks to Essential Clinical Trials......Page 321 References......Page 322 Rationale and Strategy for Development of a Malaria Vaccine......Page 325 Multistage Malaria DNA Vaccine Operation......Page 326 Preclinical Studies of Malaria DNA Vaccines in Animal Models......Page 327 Preclinical Studies Investigating Route of Administration in Animal Models......Page 328 Phase-I Clinical Trial of a PfCSP DNA Vaccine: Route of Administration......Page 329 First-Generation DNA Vaccines Are Suboptimal......Page 330 Heterologous Prime/Boost Immune Enhancement Strategies in Animal Models......Page 331 Immune Enhancement Strategies: Coadministration of Immunomodulatory Molecules......Page 333 Immune Enhancement Strategies: Modification of Target Gene for Optimal Expression in Mammalian Cells......Page 334 Genomes to Vaccines......Page 335 Acknowledgements......Page 336 References......Page 337 Introduction......Page 339 Arguments from Acquired Immunity......Page 341 Reducing Malaria Transmission May Increase Mortality and Morbidity......Page 343 Mechanisms of Malarial Pathogenesis......Page 345 Identity of the Malarial Toxin......Page 348 Biological Activities of Parasite GPIs......Page 349 GPI Appears to Be the Dominant Proinflammatory Agent of Parasite Origin......Page 350 Signal Transduction by Parasite GPIs......Page 351 Human Immune Responses to the GPI Toxin of Malaria......Page 352 GPI as a Target for Immunotherapy......Page 353 GPI as an Antidisease Vaccine Candidate......Page 354 References......Page 355 Introduction......Page 360 Definitions and Properties of Adjuvants......Page 363 Mechanisms of Adjuvants......Page 364 Freund’s Adjuvants......Page 366 Alum......Page 367 QS-21......Page 368 Montanide ISA 720......Page 369 Block Copolymer......Page 370 MPL......Page 371 CpG......Page 372 Cytokines......Page 373 Concluding Remarks......Page 374 References......Page 376 Introduction......Page 383 Vaccines for Travellers......Page 388 Vaccines for the Population of Malaria-Endemic Areas......Page 389 Justification for Taking a Candidate Antigen into Human Vaccine Trials......Page 390 Single Candidates or Combinations......Page 392 The Developmental Pathway......Page 393 Phase-I Trials......Page 395 Phase-II Trials......Page 396 Phase-III Trials......Page 398 Trial Objectives and End-Points......Page 399 Study Design......Page 400 Study Population......Page 401 End-Points......Page 402 Analysis......Page 405 After the Trial Is Over......Page 406 Phase IV......Page 407 Conclusions......Page 408 References......Page 409 Z......Page 413 A......Page 414 C......Page 415 F......Page 416 I......Page 417 M......Page 418 P......Page 419 R......Page 420 T......Page 421 V......Page 422 Z......Page 423