Co-reporter:Hui Wang;Michelle N. Griffiths;Dennis R. Burton
PNAS 2000 Volume 97 (Issue 2 ) pp:847-852
Publication Date(Web):2000-01-18
DOI:10.1073/pnas.97.2.847
We have compared the kinetics of antibody responses in conventional and dendritic cell-targeted immunization by using a model
antigen in mice. Targeting was achieved by linking the reporter antigen (polyclonal goat anti-hamster antibody) to N418, a
hamster mAb that binds to the CD11c molecule on the surface of murine dendritic cells. Intradermal injection of submicrogram
quantities of goat anti-hamster antibody complexed to mAb N418 elicited goat antibody-specific serum IgG in mice. Antigen-specific
IgG titers were detectable by day 5, with titers that ranged from 1:1000 to 1:100,000 by day 7. In contrast, when the goat
antigen was injected alone or in the presence of a hamster antibody control to form nontargeted complexes, goat-specific serum
IgG was undetectable at day 7. Additional control experiments showed that the interaction between the model antigen and mAb
N418 is required for amplification of the serum antibody response. These studies demonstrate that a single-step, facilitated-delivery
of small amounts of protein antigen to dendritic cells in vivo can give very rapid and high antibody responses. The approach may be particularly useful for vaccination immediately before
or just after exposure to a pathogen and may enhance the utility of subunit antigens as immunogens.