a novel multi-antigen virally vectored vaccine against mycobacterium avium subspecies paratuberculosis一种新型多抗原病毒载体疫苗的鸟型分支杆菌亚种副结核.pdfVIP

A Novel Multi-Antigen Virally Vectored Vaccine against Mycobacterium avium Subspecies paratuberculosis 1 2 2 1 1 1 1 Tim J. Bull , Sarah C. Gilbert , Saranya Sridhar , Richard Linedale , Nicola Dierkes , Karim Sidi-Boumedine , John Hermon-Taylor * 1 Department of Cardiovascular Sciences-Surgery, St George’s University of London, London, United Kingdom, 2 Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Background. Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal in- flammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms. Methods. We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed. Principal Findings. Vaccination ¨ of naıve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5- prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-c ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-termi