| Autor: |
Trumpfheller, Christine, Finke, Jennifer S., López, Carolina B., Moran, Thomas M., Moltedo, Bruno, Soares, Helena, Yaoxing Huang, Schlesinger, Sarah J., Chae Gyu Park, Nussenzweig, Michel C., Granelli-Piperno, Angela, Steinman, Ralph M. |
| Předmět: |
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| Zdroj: |
Journal of Experimental Medicine; 3/20/2006, Vol. 203 Issue 3, p607-617, 11p |
| Abstrakt: |
Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-20S-targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ- and interleukin 2-producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ-dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Supplemental Index |
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