title: Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A.
abstract: A replication-deficient chimpanzee adenovirus expressing Ag85A (ChAdOx1.85A) was assessed, both alone and in combination with modified vaccinia Ankara also expressing Ag85A (MVA85A), for its immunogenicity and protective efficacy against a Mycobacterium tuberculosis (M.tb) challenge in mice. Naïve and BCG-primed mice were vaccinated or boosted with ChAdOx1.85A and MVA85A in different combinations. Although intranasally administered ChAdOx1.85A induced strong immune responses in the lungs, it failed to consistently protect against aerosol M.tb challenge. In contrast, ChAdOx1.85A followed by MVA85A administered either mucosally or systemically, induced strong immune responses and was able to improve the protective efficacy of BCG. This vaccination regime has consistently shown superior protection over BCG alone and should be evaluated further.
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Stylianou
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom.
authors.forename: K L
authors.initials: KL
authors.lastname: Griffiths
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom.
authors.forename: H C
authors.initials: HC
authors.lastname: Poyntz
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Harrington-Kandt
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom.
authors.forename: M D
authors.initials: MD
authors.lastname: Dicks
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Stockdale
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Betts
authors.affiliation: The Jenner Institute, University of Oxford, United Kingdom. Electronic address: helen.mcshane@ndm.ox.ac.uk.
authors.forename: H
authors.initials: H
authors.lastname: McShane
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000261:Adenoviruses, Simian / Q000235:genetics*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D007115:Immunization Schedule; D008807:Mice, Inbred BALB C; D016896:Treatment Outcome; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D004337:Drug Carriers; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
keywords: BCG; Immunogenicity; Intranasal; Protection; Tuberculosis; Vaccine; Viral vector