FIG. 6.

Preexposure to AdHu26 dampens the transgene product-specific CD8⁺ T-cell response to an AdHu26 vector. Mice were immunized with 10¹¹ vps of an AdHu26 vector expressing the rabies virus glycoprotein. Two weeks later, sera were harvested and tested for neutralizing antibodies to AdHu26. All of the serum samples had titers in excess of 1:80. Mice were then vaccinated with 5 × 10⁹ vps of an AdHu26gag vector (Ad26/Ad26gag), and naïve control mice were vaccinated with the AdHu26gag vector at the same time (−/Ad26rab). Two weeks later, the frequencies of gag-specific CD8⁺ T cells in blood were determined. A group of naïve mice (Naive) was tested in parallel. Preexposed animals developed significantly lower responses than non-pre-exposed animals (P = 0.0007). The graph on the left shows the numbers of tetramer staining-positive CD8⁺ cells/10⁷ PBMCs. The same samples were tested for the production (+) or lack of production (−) of IFN-γ (I), MIP-1α (M), and TNF-α (T) in response to the epitope. The graph on the right shows the frequencies of CD8⁺ T cells with different cytokine profiles. The asterisk indicates a statistically significant difference in the responses of preexposed and non-pre-exposed animals.