Correlates of Vaccine-Induced Protection against Mycobacterium tuberculosis Revealed in Comparative Analyses of Lymphocyte Populations.
A critical hindrance to the development of a novel vaccine against Mycobacterium tuberculosis is a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Studies from our group and others have used a mouse-based in vitro model system to assess correlates of protection. Here, using this coculture system and a panel of whole-cell vaccines with varied efficacy, we developed a comprehensive approach to understand correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBLs) to the profiles found in immune splenocytes. PBLs not only represent a clinically relevant cell population, but comparing the expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of host responses induced when immune cells were cocultured with either the vaccine strain Mycobacterium bovis BCG or virulent M. tuberculosis. These comparisons revealed host-specific and bacterium-specific factors involved in protection against virulent M. tuberculosis. Most significantly, we identified a set of 13 core molecules induced in the most protective vaccines under all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy will facilitate vaccine development, and determining how each promotes adaptive immunity will advance our understanding of antimycobacterial immune responses.
Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Sherry L
SL
Kurtz
Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA karen.elkins@fda.hhs.gov.
Karen L
KL
Elkins
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D002417:Cattle; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D016131:Lymphocyte Subsets / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D016207:Cytokines; D032581:Tuberculosis Vaccines