Contribution of influenza immunity and virosomal-formulated synthetic peptide to cellular immune responses in a phase I subunit malaria vaccine trial.

We have demonstrated recently in a phase Ia clinical trial that synthetic malaria peptides delivered by immuno-potentiating reconstituted influenza virosomes (IRIV) induced long-lived peptide-specific antibody responses in all volunteers. In the current ancillary study to this clinical trial we have investigated the cellular immune responses specific for IRIV and the surface bound synthetic malaria peptides tested. After vaccination, in 50% (8/16) of the volunteers at least one positive lymphoproliferative response specific for the 49mer peptide derived from the Plasmodium falciparum apical membrane antigen-1 (AMA-1) was observed with stimulation indices ranging from 2 to 4.5. All volunteers showed pre-existing IRIV specific cellular immunity assessed by ex vivo IFN-gamma ELISpot analysis and lymphoproliferation. The pre-existing influenza specific T cell responses did not interfere negatively with the induction of malaria peptide-specific humoral and cellular immune responses. Our results support the view that IRIV constitute a safe antigen delivery system for induction of peptide-specific immune responses in human populations.