Perspectives for Developing New Tuberculosis Vaccines Derived from the Pathogenesis of Tuberculosis: I. Basic Principles, II. Preclinical Testing, and III. Clinical Testing
Abstract
:1. Introduction
2. Basic Principles of Resistance and Lack of Resistance to in Vivo M. tuberculosis Growth
2.1. How TB Vaccines Work
2.2. Differences between Delayed-Type Hypersensitivity (DTH) and Cell-Mediated Immunity (CMI)
2.3. Formation of Pulmonary Cavities within Which Tubercle Bacilli Grow and Evade the Immune System
2.4. TB Vaccines Cannot Prevent Reactivation of Latent TB
2.5. Mycobacterial Drug Resistance, Liquefaction of Solid Caseum and Cavity Formation
2.6. A Warning on Using TB Vaccines in Humans Who Have Already Arrested TB Lesions
3. Preclinical Testing of New TB Vaccines in Mice, Guinea Pigs and Rabbits
3.1. Tuberculosis in Humans, Mice, Guinea Pigs, Rabbits and Non-Human Primates
3.2. Balancing DTH and CMI
Vaccine in clinical trials | Type of vaccine | Protection in animal models compared to BCG vaccine | Human PPD response (DTH) | Human IFNγ response (CMI) | ||
---|---|---|---|---|---|---|
Mice | Guinea pigs | Rabbits | ||||
Phase-III | ||||||
M. vaccae | Inactivated whole cell non‐TB mycobacterium | Y | ND | ND | +/− | Y |
Mw [M. indicus pranii (MIP)] | Whole cell saprophytic non‐TB mycobacterium | Y | Y | ND | + | Y |
Phase II | ||||||
MVA85A/AERAS‐485 | Modified vaccinia Ankara vector expressing M. tbc Ag 85A | Y | Y | ND | + | Y |
AERAS‐402/CrucellAd35 | Replication‐deficient adenovirus 35 vector expressing M. tbc Ags 85A, 85B, TB10.4 | NA | ND | ND | + | Y |
M72 + AS01 | Recombinant protein composed of a fusion of M. tbc Ags Rv1196 and Rv0125 & adjuvant AS01 | EQ | EQ | EQ | + | Y |
Hybrid‐I + IC31 | Adjuvanted recombinant protein composed of M. tbc Ags 85B and ESAT‐6 [18,19,20,21,22] | EQ | EQ | ND | + | Y |
VPM 1002 | rBCG Prague strain expressing listeriolysin and carries a urease deletion mutation | Y/EQ | ND | ND | + | Y |
RUTI | Fragmented M. tbc cells | Y | Y | ND | ND | Y |
Phase-I | ||||||
rBCG30 | rBCG Tice strain expressing M. tbc Ag 30 kDa 85B | Y | Y | ND | + | Y |
M. smegmatis | Whole cell extract | NA | NA | NA | NA | Y |
AdAg85A | Replication‐deficient adenovirus 5 vector expressing M. tbc Ag 85A | Y | Y | ND | + | Y |
Hybrid‐I+CAF01 | Adjuvanted recombinant protein (M. tbc Ags 85B and ESAT‐6) | EQ | ND | ND | NA | Y |
Hybrid 56 + IC31 | Adjuvanted recombinant protein M. tbc Ags 85B, ESAT‐6 and Rv2660) | Y | ND | ND | + | Y |
HyVac4/AERAS‐404, +IC31 | Adjuvanted recombinant protein (fusion of M. tbc Ags 85B and TB10.4) | EQ | EQ | ND | + | Y |
ID93/GLA-SE | Subunit fusion protein composed of 4 M. tbc Ags | EQ | EQ | ND | + | Y |
AERAS‐422 | Recombinant BCG expressing mutated PfoA andoverexpressing M. tbc Ags 85A, 85B and Rv3407 | Y | ND | ND | ND | Y |
3.3. Producing and Counting Primary Pulmonary Tubercles in Rabbits
3.4. M. tbc Virulence Factors
3.5. Future Research Directed towards TB Latency and Reactivation
4. Ways to Improve the Clinical Testing of New TB Vaccines (Adapted from [9])
4.1. Identify a Human Population That Could Benefit from Receiving a TB Vaccine
4.2. Identify HIV-Infected Individuals
4.3. Identify Individuals with Intestinal Helminths and/or Poor Nutrition
4.4. Assess the Role of Environmental Mycobacteria
4.5. Perform Booster Tuberculin Skin Tests
4.6. Identify Antigenic Differences among TB Vaccines
4.7. Identify Human Genetic Differences
5. Conclusions
5.1. DTH and CMI
5.2. Selecting the Best New TB Vaccine
5.3. Critical Antigens
Acknowledgments
References
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Dannenberg, A.M.; Dey, B. Perspectives for Developing New Tuberculosis Vaccines Derived from the Pathogenesis of Tuberculosis: I. Basic Principles, II. Preclinical Testing, and III. Clinical Testing. Vaccines 2013, 1, 58-76. https://doi.org/10.3390/vaccines1010058
Dannenberg AM, Dey B. Perspectives for Developing New Tuberculosis Vaccines Derived from the Pathogenesis of Tuberculosis: I. Basic Principles, II. Preclinical Testing, and III. Clinical Testing. Vaccines. 2013; 1(1):58-76. https://doi.org/10.3390/vaccines1010058
Chicago/Turabian StyleDannenberg, Arthur M., and Bappaditya Dey. 2013. "Perspectives for Developing New Tuberculosis Vaccines Derived from the Pathogenesis of Tuberculosis: I. Basic Principles, II. Preclinical Testing, and III. Clinical Testing" Vaccines 1, no. 1: 58-76. https://doi.org/10.3390/vaccines1010058