Abstracts (complete list) - Wissenschaft Online

Andreas Wieland, Markus Denzel, Jörg Reimann, Reinhold Schirmbeck
In vivo produced complexes of antigen with stress proteins
are potent immunogens
To facilitate priming of T cells, stress (or heat shock) proteins of the Hsp70/90 families
have been incorporated into vaccine formulations (by loading antigenic peptides to Hsp,
or constructing Hsp/antigen fusion proteins). We expressed a chimeric protein
containing a Hsp-capturing, J-homologous domain and an antigen-encoding sequence to
produce in situ Hsp/antigen complexes. DNA vaccines expressing antigens with this
stress protein-capturing domain display enhanced immunogenicity for T and B cells.
Complexes of antigen associated with constitutively expressed Hsp73 or stress induced
Hsp70 accumulate to high steady state levels in transfected eukaryotic cells that
produce these chimeric proteins. We designed a purification method to isolate from
transfectants native Hsp/antigen complexes that efficiently elicit antigen-specific
immune responses in mice. Similar to peptide-bound Hsps these complexes facilitate
priming of CD8 T cells. The delivery of chaperone-associated antigen is thus an
attractive strategy to elicit multispecific responses of different compartments of the
immune system.