PB1 as a potential target for increasing the breadth of T-cell mediated immunity to Influenza A.

Autor: Uddbäck IE; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Steffensen MA; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Pedersen SR; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Nazerai L; 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.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2016 Oct 07; Vol. 6, pp. 35033. Date of Electronic Publication: 2016 Oct 07.
DOI: 10.1038/srep35033
Abstrakt: Recently, we showed that combined intranasal and subcutaneous immunization with a non-replicating adenoviral vector expressing NP of influenza A, strain PR8, induced long-standing protection against a range of influenza A viruses. However, H-2 b mice challenged with an influenza A strain mutated in the dominant NP 366 epitope were not efficiently protected. To address this problem, we envision the use of a cocktail of adenovectors targeting different internal proteins of influenza A virus. Consequently, we investigated the possibility of using PB1 as a target for an adenovector-based vaccine against influenza A. Our results showed that PB1 is not as immunogenic as the NP protein. However, by tethering PB1 to the murine invariant chain we were able to circumvent this problem and raise quite high numbers of PB1-specific CD8 + T cells in the circulation. Nevertheless, mice immunized against PB1 were not as efficiently protected against influenza A challenge as similarly NP-vaccinated animals. The reason for this is not a difference in the quality of the primed cells, nor in functional avidity. However, under similar conditions of immunization fewer PB1-specific cells were recruited to the airways, and surface expression of the dominant PB1 peptide, PB1 703 , was less stable than in the case of NP 366 .
Competing Interests: Together with the University of Copenhagen and Peter J Holst, the authors JPC and ART hold a patent regarding the invariant chain fusion technology.
Databáze: MEDLINE
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