However, the antibodies induced during natural hRSV infection fail to prevent recurrent infections throughout life, indicating that also the efficacy of vaccine-induced neutralizing antibodies may be limited [7] and [11]. Controversy

also exists concerning the precise role of the T cell compartment in pneumovirus-induced disease [12] and [13]. Several studies have shown that although T cells are essential in eradicating established infections [14], they also are important mediators of hRSV-induced immunopathology Selleckchem PF2341066 [15], [16], [17], [18] and [19]. In murine models, especially Th2 skewing of the CD4+ T-cell lineage after immunization with FI-RSV or hRSV-G protein encoding recombinant Vaccinia virus vectors have been shown to lead to enhanced disease following subsequent hRSV infection [12], [13] and [20]. Induction of CD8+ T-cell responses, on the other hand, inhibited vaccine-enhanced pulmonary disease [21], [22] and [23]. Thus, despite the notion that T cells play a role in pneumovirus-induced immunopathology, these studies suggest that vaccines designed to induce antipneumoviral CD8+ T cell responses may offer an alternative to vaccines targeting the humoral response. Pneumoviruses display a narrow host range and several species-specific variants

have been described [1], adapted for evasion of defense mechanisms in their specific hosts [24] and [25]. Therefore, instead of hRSV, its mouse-adapted variant PVM is increasingly

used to study pneumovirus-specific immune responses and immunopathogenesis in mouse models. PVM and hRSV display a marked genetic www.selleckchem.com/products/DAPT-GSI-IX.html similarity and use similar evasion strategies [26], [27] and [28]. Intranasal (i.n.) administration of a low PVM inoculum results in effective replication and severe respiratory disease in mice, with several hallmarks similar to severe hRSV disease in humans, including severe pulmonary inflammation, edema, and influx 4-Aminobutyrate aminotransferase of granulocytes [29]. Although extensively studied during hRSV infections in mouse models, only limited studies evaluated T cells in PVM infected mice [30] and [31]. Frey et al. showed that, like in hRSV-infection, T-cells are essential for viral elimination in PVM-infected mice, but are also important mediators of infection-associated pathology [31]. This observation raises the question of whether a pneumovirus-vaccine that targets CD8+ T cell responses would be safe. In this study, we used the PVM mouse model of respiratory infection to determine whether pre-existing virus-specific CD8+ T-cells may provide protection against pneumovirus-induced disease. PVM strain J3666 was passaged in mice to retain full pathogenicity and hRSV strain A2 was grown in BSC-1 cells and concentrated as described [32]. For both viruses, plaque assays on BSC-1 cells were performed to determine viral titers. Influenza strains A/HK/x31 (H3N2) and A/PR/8/34 (H1N1) were grown as described [33].