ADVANCES IN IMMUNOLOGY
CONTENTS 1 IMMUNOLOGY AND THE CONCEPT OF VACCINATION MANIPULATION OF THE IMMUNE SYSTEM BY VACCINATION OVERVIEW OF IMMUNITY AND THE IMMUNE SYSTEM THE CONCEPT OF IMMUNITY THE INNATE IMMUNE RESPONSE ADAPTIVE IMMUNE RESPONSE PROPHYLACTIC AND THERAPEUTIC VACCINES IMMUNOLOGIC MEMORY AND VACCINATION REFERENCES 2 VACCINE TYPES AND REVERSE VACCINOLOGY INTRODUCTION FUNDAMENTALS OF VACCINE IMMUNOLOGY CLASSES OF VACCINES WHOLE-PATHOGEN VACCINES SUBUNIT VACCINES NUCLEIC ACID VACCINES AND OTHER EXPERIMENTAL APPROACHES IMMUNOINFORMATICS REVERSE VACCINOLOGY (RV) AND OTHER APPLICATIONS 3 DENDRITIC CELLS AS VACCINE TARGETS INTRODUCTION TO DENDRITIC CELLS ORIGIN AND TYPES OF DENDRITIC CELLS CONVENTIONAL DENDRITIC CELLS MONOCYTE-DERIVED DENDRITIC CELLS PLASMACYTOID DENDRITIC CELLS CYTOKINES/GROWTH FACTORS IN DIFFERENTIATION OF DENDRITIC CELLS LOCATION OF DENDRITIC CELLS DENDRITIC CELL IN LYMPH NODES DENDRITIC CELL IN SPLEEN DENDRITIC CELL IN THYMUS DENDRITIC CELL WITHIN THE SKIN DENDRITIC CELL WITHIN THE GUT RECEPTORS OF DENDRITIC CELLS C-TYPE LECTIN RECEPTORS TOLL-LIKE RECEPTORS NOD-LIKE RECEPTORS RIG-LIKE RECEPTORS AIM2-LIKE RECEPTORS STRATEGIES FOR TARGETING VACCINES TO DENDRITIC CELL RECEPTORS FURTHER READING 4 VACCINE DEVELOPMENT: FROM THE LABORATORY TO THE FIELD ANTIGEN SELECTION FOR NEW VACCINES GENETIC STUDIES EXPRESSION OF THE ANTIGENIC TARGET GENE OF INTEREST GENETICALLY MODIFIED WHOLE ORGANISMS IN VACCINE STUDIES BASIC PROTEIN STUDIES ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) DIRECT ELISA INDIRECT ELISA COMPETITIVE ELISA SANDWICH ELISA ENDPOINT TITER ELISA MONITORING THE IMMUNE RESPONSE IN VACCINE RESEARCH WESTERN BLOTTING GENERAL WESTERN BLOT DETAILED PROTOCOL FLOW CYTOMETRY OTHER METHODS OF IN VITRO EVALUATION OF IMMUNOGENICITY CYTOKINE ANALYSIS PURIFICATION OF ANTIBODIES (IGGS) GROWTH INHIBITION ASSAY ANTIBODY-DEPENDENT CELLULAR INHIBITION ASSAY ANTIBODY-DEPENDENT RESPIRATORY BURST ACTIVITY RNA EXPRESSION ANALYSIS CONCLUSION 5 HARNESSING THE POWER OF CD81 T-CELLS: IDENTIFICATION AND VALIDATION OF PEPTIDES BOUND TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I BY IMMUNOPEPTIDOMICS CD81 T CELLS AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I ANTIGEN PRESENTATION PROTEASOME CLEAVAGE MECHANISMS INTRACELLULAR TRAFFICKING OF PEPTIDES PEPTIDE BINDING AFFINITY TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I TOOLS FOR DISCOVERING IMMUNOGENIC PEPTIDES IMMUNOPEPTIDOMICS VACCINE DESIGN BASED ON IMMUNOPEPTIDOMICS METHODS FOR THE VALIDATION OF IMMUNOGENIC PEPTIDES CONCLUSIONS ACKNOWLEDGMENTS 6 VIRUS-LIKE PARTICLE VACCINES IMMUNE RESPONSE TO VIRUS-LIKE PARTICLES PRODUCTION OF VIRUS-LIKE PARTICLES EXPRESSION SYSTEMS INSECT CELLS YEAST ESCHERICHIA COLI PLANT CELLS MANUFACTURING: UPSTREAM PROCESS MANUFACTURING: PURIFICATION OF VIRUS-LIKE PARTICLES (DOWNSTREAM PROCESS) MAJOR CONTAMINANTS AND REMOVAL STRATEGIES ANALYTICAL TOOLS FOR VIRUS-LIKE PARTICLES TOTAL PROTEIN AND PURITY ANALYSIS SIZE AND MORPHOLOGY CONFIRMATION COMPOSITION ANALYSIS 7 APPROACHES TO CANCER VACCINATION TYPES OF CANCER VACCINES WHOLE TUMOR CELL VACCINES PEPTIDE-BASED VACCINES DENDRITIC CELL VACCINES NUCLEIC ACID VACCINES DNA VACCINES MRNA VACCINES NOVEL TRENDS IN CANCER VACCINE DEVELOPMENT CANCER STEM CELL VACCINES NEOANTIGEN-BASED VACCINES CANCER VACCINE DELIVERY SYSTEMS VIRAL VECTORS NANOCARRIERS NANOPARTICLES LIPOSOMES NANOEMULSIONS SUMMARY THE COVID-19 PANDEMIC THE SPIKE PROTEIN OF THE SARS-COV-2 VIRUS COVID-19 VACCINE DEVELOPMENT NUCLEIC ACIDBASED VACCINES MESSENGER RNA VACCINES VIRAL VECTOR VACCINES ANTIGEN-PRESENTING CELL-BASED VACCINES PROTEIN-BASED VACCINES WHOLE ORGANISM-BASED VACCINES LIVE ATTENUATED VIRUS VACCINES FUTURE VACCINE REQUIREMENTS AND CHALLENGES 9 ADJUVANTS, IMMUNOMODULATORS, AND ADAPTOGENS ANITA MILICIC, SO¨ REN REINKE, JOANNAH FERGUSSON, ERIK B LINDBLAD, ANEESH THAKUR, GEORGE CORBY, STEPHANIE LONGET, SABINA GO´ RSKA, AGNIESZKA RAZIM, KEFEI HU, BROR MOREIN, MARINA LUCHNER, DENNIS CHRISTENSEN, SLAVCHO MRENOSHKI, SEBNEM ERCELEN CEYLAN, SVEINBJORN GIZURARSON AND MALACHY CHIGOZIE UGWU INTRODUCTION ANTIGEN PRESENTATION ALUMINUM-BASED ADJUVANTS ORIGIN AND CHEMICAL COMPOSITION APPLICATION MECHANISM OF ACTION TYPE OF IMMUNE RESPONSE INDUCED EMULSION-BASED ADJUVANTS SAPONINS MECHANISM OF ACTION AND TYPE OF IMMUNE RESPONSE INDUCED IMMUNE STIMULATING COMPLEXES TLR AGONISTS APPLICATION, MECHANISM OF ACTION, AND TYPE OF IMMUNE RESPONSE INDUCED EXOSOMES GSK ADJUVANT SYSTEMS CHOLERA TOXIN FREUND’S ADJUVANT ?-GALCER ADJUVANT PROPERTIES OF THE MICROBIOME PLANT-DERIVED ADAPTOGENS 10 GMP MANUFACTURE AND QUALITY CONTROL REGULATION GMP MANUFACTURE VACCINE PURIFICATION IN PROCESS CONTROLS AND FINAL RELEASE TESTING 11 TESTING VACCINES: ESSENTIAL STEPS IN CLINICAL TRIAL DESIGN VACCINE DEVELOPMENT PATHWAY INTRODUCTION TO GOOD CLINICAL PRACTICE CONSENT GOOD CLINICAL PRACTICE COMPLIANT DOCUMENTATION PARTICIPANT FACING DOCUMENTS OTHER DOCUMENTS CLINICAL TRIAL ROLES AND RESPONSIBILITIES ENSURING QUALITY DATA SAFETY MONITORING COMMITTEE TRIAL STEERING COMMITTEE SAFETY SCREENING MEDICAL COVER ADVERSE EVENTS SOLICITED AND UNSOLICITED ADVERSE EVENTS RECORDING ADVERSE EVENTS ADVERSE EVENT ASSESSMENT REPORTING REQUIREMENTS OTHER TRIAL CONSIDERATIONS REIMBURSEMENT PUBLICATION CONSIDERATIONS CONFIDENTIALITY AND DATA CONTROL FINAL WORD