Abstract
Understanding the complexity of the T-cell epitope hierarchy in humans through mouse models can be difficult. In particular, using only one murine strain, the C57BL/6 mouse, to investigate the immune response to influenza virus infection limits our understanding. In the present study, by immunizing C57BL/6 mice with an adenoviral vector encoding the polymerase acidic (AdIiPA) protein of influenza A virus, we were able to induce a high number of PA-specific T cells. However, upon challenge, these cells were only partly protective. When instead immunizing BALB/c mice with AdIiPA, we found that the immunized mice were fully protected against challenge. We found that this protection was dependent on CD8 T cells, and we identified a novel H-2Dd-restricted epitope, PA33. These findings provide a new tool for researchers to study PA-specific immunity in mice with an H-2d haplotype. Additionally, our findings underscore the importance of critically evaluating important limitations of using a single inbred mouse strain in vaccine studies.
Highlights
We found that vaccination with adenoviral vector encoding the polymerase acidic (AdIiPA) induced high numbers of PA224–233 (PA224)-specific CD8 T cells in C57BL/6 mice, but when challenged, only half of the mice were protected from lethal influenza infection
To investigate the CD8 T-cell response generated by AdIiPA vaccination, C57BL/6 mice were immunized with AdIiPA, and number of IFNγ-producing cells after PA224 stimulation was enumerated in the spleen at 11, 14, 17, 20, 30, and 60 days post-immunization
The number of PA-specific memory T cells was analyzed in the airways, lungs, spleen, and mediastinal lymph node (MLN) 60 days after vaccination as well as 5 days after influenza
Summary
The influenza A virus remains a major cause of human disease in today’s society, with up to 3 million cases of severe disease annually worldwide [1]. Point mutations in the genes encoding the surface proteins, hemagglutinin, and neuraminidase may cause conformational changes that prevent antibodies from neutralizing the virus. These changes, termed antigenic drift, give rise to new seasonal strains that force annual evaluation and reformulation of the vaccines, often resulting in vaccines with middle to low efficiency [2,3]. In difference to a neutralizing humoral response, CD8+ T cells recognize epitopes from conserved internal proteins of the virus. We have previously demonstrated that vaccination locally and systemically with an adenovirus encoding nucleoprotein (AdNP)
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