New non-replicative vectors for CTL activation

• Published in: Research in immunology (Paris) Vol. 149; no. 1; pp. 67 - 69
• Main Authors: Leclerc, C., Fayolle, C., Guermonprez, P., Ladant, D., Lo-Man, R., Rueda, P., Sarraseca, J., Saron, M.F., Sebo, P., Sedlik, C., Casal, I., Ullmann, A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 1998
• ISSN: 0923-2494
• DOI: 10.1016/S0923-2494(98)80049-7

CD8 super(+) cytotoxic T lymphocytes (CTLs) play an important role in the elimination of cells infected by pathogens and in the regression of tumours. CTLs recognize antigen-derived peptides presented by major histocompatibility (MHC) class I molecules on the cell surface and are usually activated by peptides resulting from the processing of endogenous intracellular proteins. Because antigens have to gain access to the cytosol to enter the class-I-restricted presentation pathway, exogenous soluble proteins are usually unable to stimulate CTL responses. Therefore, several strategies have been developed to deliver exogenous antigens into the cytosol. Protein or peptide antigens delivered in association with appropriate adjuvants efficiently stimulate CTL responses. However, alum (aluminium salts) is still the only adjuvant currently licensed for use in human vaccines. Several recombinant live bacterial or viral vectors have also been shown to sensitize CTLs in vivo but are risk-prone. DNA vaccination may also represent a powerful strategy to activate CTL responses, but the safety of this method remains to be determined. Therefore, the development of safe strategies to induce CTL responses with non-replicating antigens is still an important prerequisite for the design of new efficient vaccines. Recently, we have developed new and efficient non-replicative recombinant vectors able to deliver antigens into the MHC class I pathway based either on the invasive property of a bacterial toxin or on the capacity of parvovirus-like particles to deliver foreign CTL epitopes into the cytosol of cells.