No abstract

We previously demonstrated that a single dose of nonadjuvanted intranasal ␥-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed crossprotection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal heterosubtypic influenza virus challenge. Furthermore, ␥-irradiated influenza viruses induced cross-reactive Tc-cell responses but not crossneutralizing or cross-protective antibodies. In addition, histological analysis showed reduced lung inflammation in vaccinated mice compared to that in unvaccinated controls following heterosubtypic challenge. This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4؉ and CD8 ؉ , and with early influenza virus-specific cytotoxic T-cell responses. Therefore, cross-protective immunity induced by vaccination with ␥-irradiated influenza A virus is mediated mainly by Tc-cell responses.

Treatment of chronic HCV with modern DAA therapy was associated with a significant improvement in LSM by VCTE measurement, suggesting possible early improvement in liver fibrosis along with resolution of inflammation over the first year after treatment completion.