title: Incorporation of CpG oligodeoxynucleotide fails to enhance the protective efficacy of a subunit vaccine against Mycobacterium tuberculosis.
abstract: Vaccines which offer better protection than BCG are now badly needed for controlling tuberculosis infection throughout the world. Immunological adjuvants capable of inducing a TH1 type of protective response are necessary to augment the immune response, particularly in the case of subunit vaccines. It is now well established that oligodeoxynucleotides (ODN) containing cytidine phosphate guanosine (CpG) motifs enhance cell-mediated responses in vivo by increasing the production of the TH1 cytokines IL-12 and interferon gamma (IFNgamma). To determine if this would improve subunit vaccination of mice CpG ODN were added to a subunit vaccine consisting of the culture filtrate proteins (CFP) of Mycobacterium tuberculosis H37Rv. It was observed that although adding CpG ODN to the vaccines promoted substantially increased IFNgamma production by lymph node cells draining sites of inoculation, this failed to translate after aerosol challenge into any degree of enhancement of bacterial clearance in the lungs, influx of IFN-positive T cells, or changes in histopathology. These data suggest that the vaccine enhancing effects of CpG ODN are relatively transient.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Microbiology building, 1682 Campus Delivery, Fort Collins, CO 80523-1682, USA.
authors.forename: Meng-Jer
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Ana-Paula
authors.initials: AP
authors.lastname: Junqueira-Kipnis
authors.forename: A
authors.initials: A
authors.lastname: Hoeffer
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Turner
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
mesh_terms: D000818:Animals; D018899:CpG Islands; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009841:Oligonucleotides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000737:chemistry / Q000276:immunology*; D014611:Vaccination
chemical_list: D009841:Oligonucleotides; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma