Induction of cytotoxic T lymphocyte activity by fusion-active peptide-containing virosomes

Priming of cytotoxic T lymphocyte (CTL) activity with exogenous antigen req uires introduction of the antigen into the MHC class I presentation pathway of antigen-presenting cells. In the present study, we used fusogenic recon stituted envelopes (virosomes), derived from influenza virus, as a carrier system for delivery of a synthetic soluble peptide corresponding to a major murine CTL epitope of the influenza virus nucleoprotein (NP). Virosomes co ntaining encapsulated NP-peptide efficiently sensitized target cells for re cognition by influenza-specific CTLs generated through priming of mice with infectious virus. Intramuscular immunization of mice with peptide-containi ng virosomes induced a potent class I MHC-restricted CTL response against i nfluenza-infected target cells. By contrast, an equal dose of NP-peptide en capsulated in fusion-inactivated virosomes did not induce CTL activity, ind icating an essential role of the membrane fusion activity of the virosomes in the induction of the response. Likewise, NP-peptide encapsulated in lipo somes, NP-peptide mixed with empty virosomes and NP-peptide in IFA failed t o induce a CTL response. These results demonstrate that fusion-active viros omes represent a promising delivery system for induction of class I MHC-res tricted CTL activity with non-replicating viral antigens. (C) 2000 Elsevier Science Ltd. All rights reserved.