| Autor: |
Uddback IE; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Pedersen LM; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Pedersen SR; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Steffensen MA; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Holst PJ; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Thomsen AR; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Christensen JP; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. |
| Abstrakt: |
The threat from unpredictable influenza virus pandemics necessitates the development of a new type of influenza vaccine. Since the internal proteins are highly conserved, induction of T cells targeting these antigens may provide the solution. Indeed, adenoviral (Ad) vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. Local (intranasal (i.n.)) immunization elicited delayed, but more lasting protection despite relatively inefficient immunization. However, by far, the most robust protection was induced by simultaneous, combined (i.n. + s.c.) vaccination, and, notably, in this case clinical protection lasted at least 8 months without showing any evidence of fading. Interestingly, the superior ability of the latter group to resist reinfection correlated with a higher number of antigen-specific CD8 T cells in the spleen. Thus, detailed analysis of the underlying CD8 T cell responses highlights the importance of T cells already positioned in the lungs prior to challenge, but at the same time underscores an important back-up role for circulating antigen-specific cells with the capacity to expand and infiltrate the infected lungs. |
