Enhancing Antibody Responses by Targeting Vaccine Antigens to Clec9A on Dendritic Cells
Walter and Eliza Hall Institute of Medical Research
1g Royal Parade, Parkville
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Clec9A (DNGR1) is a dead cell recognition receptor on the surface of the cDC1 (CD8+; XCR1+) DC lineage in mice and humans. This receptor, and its ligand F-actin, were discovered in K.Shortman’s laboratory by Mireille Lahoud and Irina Caminschi, both now at Monash University; the project continues in collaboration with them. Antibodies (Ab) against Clec9A can be used to target antigens (Ag) to Clec9A in situ. This leads to efficient generation of cytotoxic T cells (if DC activating adjuvants are used) and to high and prolonged Ab production (even in the absence of adjuvants and DC activation). The basis of this exceptional Ab production has been determined. Such Clec9A targeting has been applied to some otherwise poorly antigenic subunit vaccine candidates for infectious diseases, and shown to greatly enhance Ab responses and provide protective immunity.
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