title: A polyvalent DNA vaccine expressing an ESAT6-Ag85B fusion protein protects mice against a primary infection with Mycobacterium tuberculosis and boosts BCG-induced protective immunity.
abstract: In this study, we evaluated the protective efficacy of a DNA vaccine (pE6/85) expressing an ESAT6-Ag85B fusion protein against a primary Mycobacterium tuberculosis infection in mice. In short-term studies, vaccination with pE6/85 protected as well as Mycobacterium bovis BCG immunization with similar lung pathology and bacterial burdens detected 28 days after a low dose aerogenic challenge (>1.0 log(10) reduction relative to naïves). In a survival experiment, the protection induced by pE6/85 immunization was also not significantly different than that elicited by BCG vaccination with the mean-times-to-death (+/-standard error of the mean) being 102+/-20, 271+/-32 and 299+/-14 days for naïve, pE6/85 and BCG-vaccinated mice, respectively. Furthermore, boosting with pE6/85 but not BCG or a DNA vaccine cocktail at 1 year after an initial BCG immunization (when BCG-induced protection was declining), augmented protection in the lung at 15 and 18 months to levels detected at 3 months post-BCG vaccination.
authors.affiliation: Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Building 29, Room 502, CBER/FDA, 29 Lincoln Drive, Bethesda, MD 20892, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Derrick
authors.forename: Amy Li
authors.initials: AL
authors.lastname: Yang
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Morris
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics*; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D051379:Mice; D009169:Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis