title: Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate.
abstract: Mycobacterium tuberculosis HN878 represents a virulent clinical strain from the W-Beijing family, which has been tested in small animal models in order to study its virulence and its induction of host immune responses following infection. This isolate causes death and extensive lung pathology in infected C57BL/6 mice, whereas lab-adapted strains, such as M. tuberculosis H37Rv, do not. The use of this clinically relevant isolate of M. tuberculosis increases the possibilities of assessing the long-lived efficacy of tuberculosis vaccines in a relatively inexpensive small animal model. This model will also allow for the use of knockout mouse strains to critically examine key immunological factors responsible for long-lived, vaccine-induced immunity in addition to vaccine-mediated prevention of pulmonary immunopathology. In this study, we show that the ID93/glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) tuberculosis vaccine candidate, currently in human clinical trials, is able to elicit protection against M. tuberculosis HN878 by reducing the bacterial burden in the lung and spleen and by preventing the extensive lung pathology induced by this pathogen in C57BL/6 mice.
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA susan.baldwin@idri.org.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Baldwin
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Reese
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Po-Wei D
authors.initials: PW
authors.lastname: Huang
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Elyse A
authors.initials: EA
authors.lastname: Beebe
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Brendan K
authors.initials: BK
authors.lastname: Podell
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA PAI Life Sciences, Inc., Seattle, Washington, USA.
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D058491:Bacterial Load; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D013154:Spleen / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic