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.
