The mode of presentation and route of administration are critical for the induction of immune responses to p53 and antitumor immunity.

We have examined the immune response to full-length wild-type human p53 presented by a recombinant canarypox vector (ALVAC) and by plasmid DNA. For the ALVAC recombinant, intravenous, but not subcutaneous, intramuscular or intradermal administration, induced CD8+ CTLs that lysed tumor cells transfected with human mutant p53. Intrasplenic administration also induced CTLs. Biodistribution studies showed that intravenously injected ALVAC localized primarily in the lung, liver and spleen, whereas intramuscularly injected virus remained predominantly at the injection site. Intradermal and intramuscular immunization with naked plasmid DNA encoding human wild-type p53 also induced a specific CTL response. DNA immunization induced complete protection against challenge with a mouse embryo fibroblast transfected with human mutant p53 and partial, but significant, protection against a transfected mastocytoma. The ALVAC recombinant induced partial protection in both models. These results suggest that recombinant ALVAC and DNA might be interesting presentation platforms for p53 to be tested in clinical studies.