Intranasal delivery of recombinant parvovirus-like particles elicits cytotoxic T-cell and neutralizing antibody responses

We previously demonstrated that chimeric porcine parvovirus-like particles (PPV:VLP) carrying heterologous epitopes, when injected intraperitoneally i nto mice without adjuvant, activate strong CD4(+) and CD8(+) T-cell respons es specific for the foreign epitopes. In the present study, we investigated the immunogenicity of PPV:VLP carrying a CD8(+) T-cell epitope from the ly mphocytic choriomeningitis virus (LCMV) administered by mucosal routes. Mic e immunized intranasally with recombinant PPV:VLP, in the absence of adjuva nt, developed high levels of PPV-specific immunoglobulin G (IgC) and/or IgA in their serum, as well as in mucosal sites such as the bronchoalveolar an d intestinal fluids, Antibodies in sera from mice immunized parenterally or intranasally with PPV:VLP were strongly neutralizing in vitro. Intranasal immunization with PW:VLP carrying the LCMV CD8(+) T-cell epitope also elici ted a strong peptide-specific cytotoxic-TT-cell (CTL) response. In contrast , mice orally immunized with recombinant PPV:VLP did not develop any antibo dy or CTL responses. We also showed that mice primed with PPV:VLP are still able to develop strong CTL responses after subsequent immunization with ch imeric PPV:VLP carrying a foreign CD8(+) T-cell epitope, These results high light the attractive potential of PPV:VLP as a safe, nonreplicating antigen carrier to stimulate systemic and mucosal immunity after nasal administrat ion.