Protection against tuberculosis with homologous or heterologous protein/vector vaccine approaches is not dependent on CD8+ T cells.

Abstract

Considerable effort has been directed to develop Mycobacterium tuberculosis vaccines to boost bacille Calmette-Guérin or for those who cannot be immunized with bacille Calmette-Guérin. We hypothesized that CD4(+) and CD8(+) T cell responses with a heterologous prime/boost vaccine approach could induce long-lived vaccine efficacy against M. tuberculosis in C57BL/6 mice. We produced an adenovirus vector expressing ID93 (Ad5-ID93) for induction of CD8 T cells to use with our candidate tuberculosis vaccine, ID93/glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE), which induces potent Th1 CD4 T cells. Ad5-ID93 generates ID93-specific CD8(+) T cell responses and induces protection against M. tuberculosis. When Ad5-ID93 is administered in a prime-boost strategy with ID93/GLA-SE, both CD4(+) and CD8(+) T cells are generated and provide protection against M. tuberculosis. In a MHC class I-deficient mouse model, all groups including the Ad5-ID93 group elicited an Ag-specific CD4(+) T cell response and significantly fewer Ag-specific CD8(+) T cells, but were still protected against M. tuberculosis, suggesting that CD4(+) Th1 T cells could compensate for the loss of CD8(+) T cells. Lastly, the order of the heterologous immunizations was critical. Long-lived vaccine protection was observed only when Ad5-ID93 was given as the boost following an ID93/GLA-SE prime. The homologous ID93/GLA-SE prime/boost regimen also induced long-lived protection. One of the correlates of protection between these two approaches was an increase in the total number of ID93-specific IFN-γ-producing CD4(+) T cells 6 mo following the last immunization. Our findings provide insight into the development of vaccines not only for tuberculosis, but other diseases requiring T cell immunity.

• Authors: Susan L Baldwin, Lance K Ching, Samuel O Pine, Magdalini Moutaftsi, Elyse Lucas, Aarthy Vallur, Mark T Orr, Sylvie Bertholet, Steven G Reed, Rhea N Coler
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 191 Issue 5 Pg. 2514-2525 (Sep 01 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 23904160 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Antigens, Bacterial
• Recombinant Fusion Proteins
• Tuberculosis Vaccines

Topics

• Adenoviridae (genetics)
• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antigens, Bacterial (immunology)
• Blotting, Western
• CD8-Positive T-Lymphocytes (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Genetic Vectors
• Immunization, Secondary (methods)
• Mice
• Mice, Inbred C57BL
• Mycobacterium tuberculosis
• Recombinant Fusion Proteins (immunology)
• Tuberculosis (immunology, prevention & control)
• Tuberculosis Vaccines (immunology)