CD8 positive lymphocytes (TCD8+ play an important role in host immunity to viruses and other intracellular parasites. Anti-viral TCD8+ recognize peptides derived from a cytosolic pool of viral proteins. Induction of anti-viral TCD8+ responses is limited by the requirement that the antigen be delivered to the cytosol of antigen presenting cells in vivo. Using infectious vaccines, this is accomplished as part of the infectious cycle of the immunogen. Non-infectious vaccines (inactivated virus, subviral preparations) often fail to induced TCD8+ responses due to their inability to deliver antigens to the cytosol. It should be possible, however, to induce TCD8+ responses to non-infectious antigens. if the antigen is modified in such a way as to allow its efficient delivery to the cytosol. To explore this vaccine strategy, we studied a model antigen (ovalbumin) that we chemically conjugated to folic acid. By targeting proteins to folic acid receptors, it is believed that this modification facilitates the delivery of proteins to the cytosol. In the past year we have studied the presentation of folic acid-conjugated ovalbumin to ovalbumin-specific TCD8+. Our preliminary findings suggest that this strategy might be useful for induction of TCD8+ responses to simple protein antigens.
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