title: Immunogenicity without Efficacy of an Adenoviral Tuberculosis Vaccine in a Stringent Mouse Model for Immunotherapy during Treatment.
abstract: To investigate if bacterial persistence during TB drug treatment could be overcome by modulation of host immunity, we adapted a clinically-relevant model developed for the evaluation of new drugs and examined if immunotherapy with two adenoviral vaccines, Ad35-TBS (AERAS-402) and Ad26-TBS, could shorten therapy in mice. Even though immunotherapy resulted in strong splenic IFN-γ responses, no effect on bacterial replication in the lungs was seen. Multiplex assay analysis of lung samples revealed the absence of cytokine augmentation such as IFN-γ, TNF-α and IL-2, suggesting that immunization failed to induce immunity in the lungs. In this model, we show that IFN-γ levels were not associated with protection against disease relapse. The results obtained from our study raise questions regarding the traits of protective TB immunity that are relevant for the development of future immunotherapeutic and post-exposure vaccination strategies.
authors.affiliation: Crucell Holland B.V., Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: S Anisah
authors.initials: SA
authors.lastname: Alyahya
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Nolan
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Cara M R
authors.initials: CM
authors.lastname: Smith
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; HHMI, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
authors.affiliation: Crucell Holland B.V., Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Jerald
authors.initials: J
authors.lastname: Sadoff
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Gyanu
authors.initials: G
authors.lastname: Lamichhane
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D058491:Bacterial Load; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D007114:Immunization; D007167:Immunotherapy; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D017211:Treatment Failure; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D032581:Tuberculosis Vaccines