TARGETING DNA VACCINES TO B CELLS AS PRIMARY ANTIGEN PRESENTING CELLS

摘要

It is disclosed herein that B cells, not dendritic cells or myeloid-derived populations, are primary human antigen presenting cells for plasmid DNA. Based on this finding, improved methods and compositions for administering DNA vaccines are disclosed. Specifically, DNA vaccines are co-administered with a B cell targeting agent, B-cell recruiting agent, or a monocyte or dendritic cell recruiting agent. To increase the immunogenicity of the DNA vaccines, the B cell targeting agent or B cell recruiting agent is administered at the same location where the DNA vaccine is administered. In contrast, the monocyte or dendritic cell recruiting agent can be administered in a different location, in order to recruit cells competing with the B cells for DNA uptake away from the location where the DNA vaccine is administered.

主权项

1. A method for activating antigen-specific CD8+ T cells against a target cell type in a human subject, the method comprising:
(a) administering to the subject an effective amount of a nucleic acid-based vaccine comprising a polynucleotide encoding an antigen, and a B cell targeting agent, whereby uptake of the polynucleotide by B cells is increased relative to uptake of the polypeptide in the absence of the B cell targeting agent; or (b) administering to the subject an effective amount of a nucleic acid-based vaccine comprising a polynucleotide encoding an antigen; and co-administering to the subject a B cell recruiting agent at the same location where the nucleic acid-based vaccine is administered, whereby uptake of the polynucleotide by B cells is increased relative to uptake or expression of the polypeptide in the absence of the B cell recruiting agent; or (c) administering to the subject an effective amount of a nucleic acid-based vaccine comprising a polynucleotide encoding an antigen, and co-administering to the subject a monocyte or dendritic cell recruiting agent at a different location from where the nucleic acid-based vaccine is administered, whereby uptake of the polynucleotide by competing cell populations is decreased relative to uptake in the absence of the monocyte or dendritic cell recruiting agent.