This book reviews successes and (remaining) challenges in vaccine development for the selected Neglected Tropical Diseases (NTD) of Leprosy, Leishmaniasis, Meliodoisis and Tuberculosis, which are a continuous burden for millions of people in affected areas worldwide. Written by frontline researchers, the volume deep-dives into different vaccine strategies, provides biotechnological background information and also tackles animal models in NTD therapeutics research. By bringing together state-of-the-art expert knowledge, the book contributes to the aim of ultimately ending the epidemics of neglected tropical diseases, complying with UN Sustainable Development Goal 3, Health and Well-Being.
The volume highlights the activities of the research network VALIDATE (VAccine deveLopment for complex Intracellular neglecteD pAThogEns), funded by the Medical Research Council in the UK. The four NTDs discussed in the book were selected as these are in the focus of VALIDATE’s research.The book targets scientists and clinicians working on NTDs, as well as all readers with a background in biomedicine and interest in vaccine development.
This is an open access book.
Author(s): Myron Christodoulides
Publisher: Springer
Year: 2023
Language: English
Pages: 336
City: Cham
Contents
Chapter 1: Introduction
1.1 Neglected Tropical Diseases and the VALIDATE Pathogens
1.2 Book Synopsis
References
Chapter 2: The VALIDATE Network: Accelerating Vaccine Development for Tuberculosis, Leishmaniasis, Melioidosis and Leprosy
2.1 Introduction
2.2 VALIDATE’s Focus Pathogens
2.2.1 Tuberculosis (TB)
2.2.2 Leishmaniasis
2.2.3 Melioidosis
2.2.4 Leprosy (Hansen’s Disease)
2.3 VALIDATE: Outputs and Successes
2.3.1 Pump-Priming Funding
2.3.2 Fellowships
2.3.2.1 Dr. Jomien Mouton, Stellenbosch University (South Africa): Identification of Latency Associated Antigens and Biosignatures Associated with Mycobacterium tuberculosis
2.3.2.2 Dr. Rachel Tanner, University of Oxford (UK): Characterising the BCG-Induced Antibody Response to Inform the Design of Improved Vaccines Against M. tuberculosis, M. leprae and M. bovis
2.3.3 Training Grants
2.3.4 Mentoring
2.3.5 ECR Career Development Network
2.3.6 Information Dissemination
2.3.7 Events
2.3.8 Outreach
2.3.9 Data Sharing
2.3.10 Equipment Exchange
2.4 The Future of VALIDATE
References
Part I: Leprosy and Buruli Ulcer
Chapter 3: A Current Perspective on Leprosy (Hansen’s Disease)
3.1 Introduction
3.2 Disease Transmission and Infection
3.3 Disease Classification and Pathophysiology
3.4 Diagnosis and Treatment
3.5 Challenges and Future Direction
3.5.1 The WHO Roadmap
3.5.2 Stigma and Discrimination
3.5.3 Alternative Therapies
3.5.4 Animal and Ex Vivo Models
3.5.5 Diagnostics
3.5.6 M. leprae Vaccine
3.6 Conclusions
References
Chapter 4: Leprosy Vaccines: Developments for Prevention and Treatment
4.1 Introduction
4.2 The BCG Vaccine Has Variable Protection Against Leprosy
4.3 The Recombinant BCG Vaccines to Improve Efficacy Against Leprosy
4.4 The Cross-Reactivity and Subunit Leprosy Vaccines
4.5 Vaccine and Drug Combinatory Therapy
4.6 Conclusion and Vaccine Outlook
References
Chapter 5: Current Progress and Prospects for a Buruli Ulcer Vaccine
5.1 Buruli Ulcer
5.1.1 Epidemiology and Transmission
5.1.2 Clinical Presentations and Current Treatments
5.2 Mycobacterium ulcerans
5.2.1 Mycolactone
5.2.2 Immune Response to M. ulcerans Infection
5.3 Vaccine Candidates
5.3.1 Human Studies with BCG
5.3.2 Mouse Studies of BU Vaccine Candidates
5.3.2.1 Whole Bacteria Vaccines
5.3.2.2 Subunit Vaccines for BU
5.4 Prospects
References
Part II: Tuberculosis
Chapter 6: Correlates of Protection from Tuberculosis
6.1 Introduction
6.2 Innate Immunity
6.2.1 Early Clearance and a Role for Innate Immunity
6.2.2 Mononuclear Phagocytes
6.2.3 Natural Killer Cells
6.2.4 Neutrophils
6.2.5 Donor Unrestricted T Cells
6.2.6 Trained Innate Immunity
6.3 Conventional T Cells
6.3.1 CD4+ T Cells
6.3.1.1 IFN-γ Producing CD4+ T Cells
6.3.1.2 Polyfunctional CD4+ T Cells
6.3.1.3 Th17 Cells
6.3.2 CD8+ T Cells
6.4 Humoral Immunity
6.4.1 B Cells
6.4.2 Antibodies
6.5 Approaches to Identifying Correlates of Protection
6.5.1 Preclinical Models
6.5.1.1 Murine Models
6.5.1.2 Guinea Pigs
6.5.1.3 Cattle
6.5.1.4 Non-human Primates (NHPs)
6.5.1.5 Novel Humanized Animal Models
6.5.2 Clinical Studies
6.5.2.1 Clinical TB Vaccine Trials
6.5.2.2 Observational Studies
6.5.3 Controlled Human Infection Models
6.5.3.1 PPD CHIMs
6.5.3.2 BCG CHIMs
6.5.3.3 Other CHIM Models
6.5.4 Mycobacterial Growth Inhibition Assays
6.6 Conclusion
References
Chapter 7: Animal Models of Tuberculosis
7.1 Introduction
7.2 Mouse (Order Rodentia, Family Muridae, Mus musculus)
7.3 Rat (Order Rodentia, Family Muridae, Rattus norvegicus)
7.4 Rabbit (Order Lagomorpha, Family Leporidae, Oryctolagus cuniculus)
7.5 Zebrafish (Order Cypriniformes, Family Cyprinidae, Subfamily Danioninae, Danio rerio)
7.6 Cattle (Order Artiodactyla, Family Bovidae, Subfamily Bovinae, Bos taurus)
7.7 Guinea Pigs (Order Rodentia, Family Caviidae, Cavia, C. porcellus)
7.8 Non-Human Primates
7.9 Other Models
7.9.1 Cat (Order Carnivora, Family Felidae, Felis catus)
7.9.2 Dog (Order Carnivora, Family Canidae, Canis familiaris)
7.9.3 Deer (Order Artiodactyla, Family Cervidae, Genus cervus)
7.9.4 Minipig (Order Artiodactyla, Family Suidae, Sus domesticus)
7.9.5 Fruit Fly (Order Diptera, Family Drosophilidae, Drosophila melanogaster)
7.10 Conclusions and Perspectives
References
Chapter 8: BCG: Past, Present and Future Direction
8.1 History of BCG
8.2 Evolution and Genetics of BCG Vaccines
8.3 Immunogenicity of BCG
8.3.1 Innate Immune Responses
8.3.2 Adaptive Immune Response
8.3.3 Trained Immunity
8.4 Efficacy of BCG Against TB
8.4.1 Reasons for Variable BCG Efficacy
8.4.2 BCG Revaccination
8.4.3 Measuring BCG Protection?
8.5 Efficacy of BCG Against Other Infections
8.5.1 BCG and Other Mycobacterial Infections
8.5.2 BCG “Non-Specific” Immunity
8.5.3 BCG and COVID-19 Disease
8.6 BCG and Non-Communicable Diseases
8.6.1 BCG and Cancer
8.6.2 BCG and Allergic, Autoimmune and Inflammatory Diseases
8.7 Safety and Adverse Effects of BCG
8.8 BCG Future Directions
8.8.1 Recombinant BCG
8.8.2 Route of Administration
8.9 Conclusions
References
Chapter 9: The Role of Fermentation in BCG Manufacture: Challenges and Ways Forward
9.1 The BCG Vaccine: History and Approval
9.2 How Is BCG Vaccine Cultured and Manufactured: Fundamental Limitations?
9.3 Could Fermentation Be an Approach for BCG Vaccine Production?
9.4 BCG Product Characterisation
9.5 Regulatory Considerations
9.6 Concluding Remarks
References
Chapter 10: Progress in the Development of New Vaccines Against Tuberculosis
10.1 Immunological Characteristics and Markers for Mycobacterium tuberculosis
10.2 Approaches for TB Vaccine Development
10.3 Live Attenuated TB Vaccines
10.4 Inactivated TB Vaccines
10.5 Subunit TB Vaccines with Adjuvants
10.6 Recombinant TB Vaccines
10.7 Recombinant Vaccine Candidates Based on M. tuberculosis-Specific Antigens
10.8 Routes of Vaccine Delivery
10.9 Conclusion
References
Part III: Leishmaniasis
Chapter 11: Visceral and Tegumentary Leishmaniasis
11.1 Introduction
11.2 What Are Visceral Leishmaniasis and Tegumentary Leishmaniasis?
11.3 The Global Distribution of VL and TL
11.4 Current Treatment Regimens for VL and TL
11.5 An Introduction to Vaccine Development for VL and TL
11.6 Conclusions
References
Chapter 12: The Utility of a Controlled Human Infection Model for Developing Leishmaniasis Vaccines
12.1 Introduction
12.1.1 Leishmaniasis: A Vaccine-Preventable Disease
12.1.2 The Case for Controlled Human Infection
12.2 Historical Perspective of Experimental Human Infections with Leishmania
12.2.1 The Early Years and Leishmanization: From Community to Mass Usage
12.2.2 Using Leishmanization for Vaccine Evaluation
12.3 Ethical, Regulatory and Scientific Advances to Incorporate in a Modern-Day CHIM
12.3.1 The Importance of Vector Transmission
12.3.2 Regulatory Standards and Other Risk Mitigation
12.4 A Leishmania major CHIM Initiated by Sand Fly Bite
12.5 Accommodating Diversity: Leishmania CHIMs in Endemic Country Settings
12.5.1 CHIMs Using Other Leishmania Strains (Including Genetically Modified Strains)
12.5.2 Sand Fly Diversity and Other Confounders
12.6 Prospects
References
Chapter 13: Vaccines for Canine Leishmaniasis
13.1 Introduction
13.2 Diagnosis of CanL
13.3 Treatment of CanL
13.4 Immune Responses in CanL
13.5 CanL Vaccines
13.5.1 Leish-Tec® Vaccine
13.5.2 Leishmune® Vaccine
13.5.3 CaniLeish® Vaccine
13.5.4 LetiFend® Vaccine
13.5.5 New Unlicensed Vaccine Candidates for CanL
13.6 Conclusions
References
Chapter 14: Vaccine Development for Human Leishmaniasis
14.1 History of Human Leishmaniasis Vaccines
14.2 Strategies to Vaccine Design: Where Are Good Candidates to Be Found and How Do We Explore Their Potential?
14.3 Immunological Insights into Vaccine Development
14.4 Lessons from the COVID Era: What Have We Learned, and How Can We Translate It to Leishmania Vaccines?
14.5 Conclusions
References
Part IV: Melioidosis
Chapter 15: Vaccine Development Against Melioidosis
15.1 Melioidosis
15.2 Pathogenesis and Host Response
15.3 Vaccine Development
15.3.1 Live-Attenuated Vaccines
15.3.2 Inactivated Whole-Cell Vaccines
15.3.3 Subunit Vaccines
15.4 Conclusions
References
