Induction of CD8+ T-lymphocyte responses to a secreted antigen of Mycobacterium tuberculosis by an attenuated vaccinia virus.

Journal article

Protective immunity against Mycobacterium tuberculosis infection requires the activation of mycobacterium-specific CD8+ T cells, as well as CD4+ T cells. Therefore, optimizing strategies that stimulate CD8+ T cells recognizing dominant mycobacterial antigens, including secreted proteins, may lead to the development of more effective vaccines against tuberculosis. To generate a viral vaccine that is safe in humans, the early secreted protein, MPT64, was expressed in the attenuated vaccinia virus (VV) strain, modified vaccinia virus Ankara (MVA-64). The immunogenicity of MVA-64 was compared with that of the Western Reserve strain of VV (VVWR-64). The replication-defective MVA-64 was as efficient as VVWR-64 in inducing specific antibodies and cytolytic T-cell responses to a defined H-2-Db-restricted epitope on MTP-64. In addition, priming with MPT64-expressing plasmid DNA (DNA-64), and boosting with either MVA-64 or VVWR-64, markedly enhanced MPT64-specific cytolytic and IFN-gamma-producing CD8+ T-cell responses. These findings suggest that MVA may be a suitable vaccine carrier for stimulating mycobacterium-specific CD8+ T-cell responses and may be particularly relevant for developing vaccines for use in regions endemic for tuberculosis and HIV infection.

Authors: Feng, C; Blanchard, T; Smith, G; Hill, A; Britton, W

• Publication status: Published
• Journal: Immunology and cell biology
• Volume: 79
• Issue: 6
• Pages: 569-575
• Publication date: 2001-12-01
• DOI: 10.1046/j.1440-1711.2001.01042.x
• EISSN: 1440-1711
• ISSN: 0818-9641
• Language: English
• Keywords: Mycobacterium tuberculosis; Lymphocyte Activation; Vaccinia virus; Mice, Inbred C57BL; BCG Vaccine; Antigens, Bacterial; Viral Vaccines; Female; Mice; Animals; Vaccines, Attenuated; CD8-Positive T-Lymphocytes; Tuberculosis; Humans; AIDS-Related Opportunistic Infections