title: A heterologous DNA priming-Mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65, and Apa antigens improves protection against tuberculosis in mice.
abstract: Tuberculosis is responsible for >2 million deaths a year, and the number of new cases is rising worldwide. DNA vaccination combined with Mycobacterium bovis bacillus Calmette Guerin (BCG) represents a potential strategy for prevention of this disease. Here, we used a heterologous prime-boost immunization approach using a combination of DNA plasmids and BCG in order to improve the efficacy of vaccination against Mycobacterium tuberculosis infection in mice. As model antigens, we selected the M. tuberculosis Apa (for alanine-proline-rich antigen) and the immunodominant Hsp65 and Hsp70 mycobacterial antigens combined with BCG. We demonstrated that animals injected with a combination of DNA vectors expressing these antigens, when boosted with BCG, showed increased specific antimycobacterial immune responses compared to animals vaccinated with BCG alone. More importantly, the protection achieved with this regimen was also significantly better than with BCG alone.
authors.affiliation: The National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom. tricard@nimr.mrc.ac.uk
authors.forename: Jose C
authors.initials: JC
authors.lastname: Ferraz
authors.forename: Evangelos
authors.initials: E
authors.lastname: Stavropoulos
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Steve
authors.initials: S
authors.lastname: Coade
authors.forename: Clara
authors.initials: C
authors.lastname: Espitia
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Lowrie
authors.forename: M Joseph
authors.initials: MJ
authors.lastname: Colston
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Tascon
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014376:Tuberculosis / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma; D018833:Chaperonins