Principles and Guidelines for Developing Better Tuberculosis Vaccines

doi:10.1128/9781555815684.ch22

Chapter 22 : Principles and Guidelines for Developing Better Tuberculosis Vaccines

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Affiliations: 1: Center for Tuberculosis Research Departments of Environmental Health Sciences, Molecular Microbiology and Immunology, and Epidemiology, Bloomberg School of Public Health Department of Pathology, School of Medicine Johns Hopkins University, Baltimore, Maryland 21205

Content Type: Monograph

Publication Year: 2006

Category: Clinical Microbiology; Bacterial Pathogenesis

Book DOI: 10.1128/9781555815684

Chapter DOI: 10.1128/9781555815684.ch22

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Abstract:

Tuberculosis vaccines have little or no effect on the establishment of a microscopic pulmonary lesion produced by the inhalation of a virulent tubercle bacillus. Such a lesion is established only when the pulmonary alveolar macrophages fail to destroy the inhaled bacillus. Alveolar macrophages do not expand their population in response to specific antigens. Therefore, the establishment of a microscopic pulmonary tubercle is not affected by vaccination. Effective tuberculosis vaccines may, however, stop the progression of a tiny established lesion, because the vaccination has expanded antigen-specific lymphocyte populations. These lymphocytes enter the early lesion, where they cause a rapid local delayed-type hypersensitivity (DTH) and cell-mediated immunity (CMI) response that often prevents progression of the disease. When comparing their relative efficacies, two or more live vaccines should be standardized for equal numbers of live and dead bacilli, equal numbers of log-phase and dormant bacilli, and equal numbers of clumps and isolated bacilli. If vaccines more effective than BCG are ever developed, they would probably produce in the host a higher CMI/DTH ratio, i.e., an expanded antigen-specific lymphocyte population capable of producing increased numbers of activated macrophages and decreased amounts of tissue necrosis. To do this, the improved vaccine would probably contain increased bacillary glycolipid-protein components and decreased tissue-damaging tuberculin-like protein components. The vaccine should also contain components that increase the Th1/Th2 ratio. Dendritic cell-vaccine carriers may find their best use as immunotherapy in immunocompetent patients with multidrugresistant tuberculosis.

Citation: Dannenberg, Jr. A. 2006. Principles and Guidelines for Developing Better Tuberculosis Vaccines, p 341-353. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch22

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Tables

Principles and Guidelines for Developing Better Tuberculosis Vaccines

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TABLE 1

Benefits of tuberculosis vaccines producing strong CMI and weak DTH, especially those producing little or no tuberculin sensitivity^a

TABLE 1

Benefits of tuberculosis vaccines producing strong CMI and weak DTH, especially those producing little or no tuberculin sensitivity^a