Vaccinology and Methods in Vaccine Research

Vaccinology and Methods in Vaccine Research is a combination of cutting-edge methodologies, experimental approaches and literature reviews. The book covers all aspects of vaccine development, including basic immunology (focusing on the stimulation of adaptive immunity, which is required for vaccine efficacy), approaches to vaccine design and target validation, vaccine biomanufacturer and clinical development. Existing vaccinology resources are theoretical reference books, whereas this book provides a practical handbook for use in the research lab and classroom by those working in vaccinology and training others in the field. It is authored and edited by scientists actively engaged in vaccine research and development for day-to-day teaching/methodological advice. Addresses how to design a vaccine for an emerging disease, from a practical point-of -view, with chapters written by scientists who are grappling with these questions Provides new approaches to vaccine development. including vaccine targeting and virus-like-particle vaccines Gives up-to-date information and methodologies in use for vaccine adjuvants Front Cover Vaccinology and Methods in Vaccine Research Copyright Page Contents List of contributors Preface Acknowledgements 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 Cells of the innate immune system Monocytes and macrophages Macrophages Dendritic cells (DCs) Neutrophils Eosinophils Basophils Natural killer cells Natural killer T cells Secreted proteins Cytokines Interferons Interleukins Chemokines The complement system The classical pathway The alternative pathway The lectin pathway Regulation of complement activation Adaptive immune response B and T lymphocytes Cell-mediated adaptive immune responses T lymphocytes Classes of T cell The major histocompatibility complex (MHC) locus Types of MHC protein and antigen presentation MHC I CD8 MHC class II CD4 MHC class III Humoral (antibody mediated) adaptive immune response B lymphocytes: origin and differentiation Structure of immunoglobulins Immunoglobulin classes Human monoclonal antibodies as therapeutic agents 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 Live-attenuated vaccines Inactivated vaccines Subunit vaccines Toxoid vaccines Conjugate vaccines Nucleic acid vaccines and other experimental approaches DNA vaccines Viral vector vaccines RNA vaccines Immunoinformatics Reverse vaccinology (RV) and other applications References 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 Mannose receptor or CD206 DC-SIGN DEC-205 Dectin-1 family Dectin-1 The dendritic cell immune-activating receptor Lectin-like oxidized low-density lipoprotein receptor-1 CLEC-1 CLEC-2 Myeloid inhibitory C-type lectin-like receptor CLEC9A Dectin-2 family Dectin-2 Clecsf8 Dendritic cell immune receptor The blood dendritic cell antigen 2, or Clec4C Macrophage-inducible C-type lectin Toll-like receptors PAMP recognition by toll-like receptors TLR1, TLR2, and TLR6 TLR3 TLR4 TLR5 TLR7 and TLR8 TLR9 TLR11 TLR12 Toll-like receptor signaling pathways MyD88-dependent pathway TRIF-dependent pathway T cell responses stimulated by toll-like receptors NOD-like receptors NOD1 and NOD2 NOD-like receptor inflammasomes NLRP3/NALP3 inflammasome NLRP1/NALP1 inflammasome NLRC4 /NAIP (IPAF) inflammasome RIG-like receptors AIM2-like receptors Strategies for targeting vaccines to dendritic cell receptors In vivo dendritic cell targeted vaccines Ligand-based dendritic cell–targeted vaccines Antibody-based dendritic cell–targeted vaccines References Further reading 4 Vaccine development: from the laboratory to the field Introduction Antigen selection for new vaccines Genetic studies Expression of the antigenic target gene of interest Cloning of the target antigen of interest Protocol Expression and purification of the recombinant antigen Protocol Genetically modified whole organisms in vaccine studies Designing genetically engineered live-attenuated vaccines Evaluation of a genetically attenuated parasite as an engineered live-attenuated vaccine 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 General sandwich ELISA protocol Materials and methods Preparation of samples Sandwich ELISA procedure Data analysis Western blotting Detection of antibodies postvaccination and antigenic targets in vitro using western blotting General western blot detailed protocol Sample preparation Western blot procedure Gel electrophoresis protocol Protocol for transfer of proteins Immunostaining protocol Flow cytometry General flow cytometry protocol Materials Flow cytometry procedure Other methods of in vitro evaluation of immunogenicity Cytokine analysis Materials Sample preparation Procedure Purification of antibodies (IgGs) Growth inhibition assay Materials Sample preparation Procedure Data analysis Antibody-dependent cellular inhibition assay Materials Sample preparation Procedure Data analysis Antibody-dependent respiratory burst activity RNA expression analysis Conclusion References Further reading 5 Harnessing the power of CD8+ T-cells: identification and validation of peptides bound to major histocompatibility complex... CD8+ 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 References 6 Virus-like particle vaccines Introduction 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 Conclusion References 7 Approaches to cancer vaccination Introduction 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 References 8 Vaccines against SARS-CoV-2 The COVID-19 pandemic The spike protein of the SARS-CoV-2 virus COVID-19 vaccine development Nucleic acid–based vaccines DNA vaccines Messenger RNA vaccines Viral vector vaccines Antigen-presenting cell-based vaccines Protein-based vaccines Virus-like particles Protein subunit Whole organism-based vaccines Live attenuated virus vaccines Inactivated virus vaccines Future vaccine requirements and challenges References 9 Adjuvants, immunomodulators, and adaptogens Introduction Antigen presentation Antigen stabilization Right place, right time Immunogenicity Dose sparing Application Aluminum-based adjuvants Origin and chemical composition Application Mechanism of action Type of immune response induced Emulsion-based adjuvants Origin and chemical composition Application Mechanism of action Saponins Origin and chemical composition Application Mechanism of action and type of immune response induced Immune stimulating complexes Origin and chemical composition Application Mechanism of action and type of immune response induced TLR agonists Origin and chemical composition Application, mechanism of action, and type of immune response induced TLR3 agonists TLR4 agonists TLR5 agonist TLR7/8 agonists TLR9 agonists Nanoparticles Origin and chemical composition Application Mechanism of action and type of immune response induced Liposomes Origin and chemical composition Application Mechanism of action Type of immune response induced Exosomes Origin and chemical composition Application Mechanism of action and type of immune response induced GSK adjuvant systems Origin and chemical composition Application, mechanism of action, and type of immune response induced AS01 AS03 AS04 Cholera toxin Origin and chemical composition Application Mechanism of action Type of immune response induced Freund’s adjuvant Origin and chemical composition Application Mechanism of action α-GalCer Origin and chemical composition Application Mechanism of action Adjuvant properties of the microbiome Plant-derived adaptogens References 10 GMP manufacture and quality control Introduction Regulation GMP manufacture Vaccine purification In process controls and final release testing References 11 Testing vaccines: essential steps in clinical trial design Introduction Vaccine development pathway Introduction to good clinical practice Consent Good clinical practice compliant documentation Participant facing documents Participant information sheet Consent form Other documents Case report forms Contracts Standard operating procedures 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 Causality (relatedness) Severity Seriousness (serious adverse events) Reporting requirements Other trial considerations Reimbursement Publication considerations Confidentiality and data control Final word References Index Back Cover