Abstracts (complete list) - Wissenschaft Online

Annette I. Garbe, Jerome P. Jayasekera, Michael C. Carroll, Harald von Boehmer
T cell vaccination with DEC-205-influenza hemagglutinin
fusion antibodies
Current influenza vaccines are known to induce antibodies to hemagglutinin (HA) and
neuraminidase but less is known about their ability to induce cytolytic CD8 T cells to HA
determinants. In the present study we have compared UV-inactivated influenza virus
and HA delivered to dendritic cells by DEC-205 fusion antibodies in their ability to
induce T cell memory. When analysing the generation of CD8 memory cells with a
transgenic receptor for HA the DEC-205-HA fusion antibodies were found to be
somewhat superior to UV-influenza virus. Moreover in wt BALB/c mice the fusion
antibodies induced long term CD8 memory cells that developed into potent effector cells
exhibiting cytolytic activity and IFN-gamma secretion after rechallenge with UVinactivated
virus. On the other hand a single shot of DEC-205-HA fusion antibodies did
not induce HA-specific antibodies whereas UV-inactivated virus did. Nevertheless the
fusion-antibody vaccination increased HA-specific IgG2a, IgG2b and IgG1 antibodies if
given prior to challenge with inactivated virus. Finally, in preliminary experiments a
single dose of DEC-205-HA elicited protection against A/PR/8 virus. The results show
that the HA-fusion antibody induces effective CD4 and CD8 T cell memory against
influenza. This approach should be very useful for inducing T cell memory to cellinternal
viral proteins of which only peptides are presented on the cell surface of
infected cells and which are not subject to high mutation rates.