Influenza virosomes enhance class I restricted CTL induction through CD4+ T cell activation

• Published in: Vaccine 2004-01, Vol.22 (5-6), p.714-723
• Main Authors: Schumacher, Reto, Adamina, Michel, Zurbriggen, Rinaldo, Bolli, Martin, Padovan, Elisabetta, Zajac, Paul, Heberer, Michael, Spagnoli, Giulio C.
• Format: Article
• Language: English
• Subjects: Adjuvance; Adjuvants, Immunologic; Applied microbiology; Biological and medical sciences; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell culture; Cell Differentiation; Cell Division; Cells, Cultured; Centrifugation, Density Gradient; CTL; Cytotoxicity; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression - immunology; Genes, MHC Class I - genetics; Humans; Immune response; Immunity, Cellular - immunology; Immunotherapy; Influenza A virus - immunology; Influenza Vaccines - immunology; Influenza virus; Liposomes; Lymphocyte Activation - physiology; Lymphocytes; Melanoma; Microbiology; Peptides; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; T-helper 1; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Helper-Inducer - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral Proteins - immunology; Virosomes; Virosomes - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2003.08.019

Immunopotentiating reconstituted influenza virosomes (IRIV) are one of the few adjuvants currently licensed for human use. While their adjuvant capacity in the induction of humoral responses is clearly documented, few data exist on their effects on T cell immune response. Here we addressed IRIV adjuvance in the induction of HLA class I restricted cytotoxic T lymphocytes (CTL) in vitro. Lymphocyte stimulation with IM58–66 and IRIV resulted in marked expansion of specific CTL as compared to cultures performed in the presence of either antigen alone or antigen and control liposomes (L). Studies addressing underlying adjuvant mechanisms demonstrated that IRIV activated CD4/CD45RO+ T cells, induced a cytokine profile consistent with T helper 1 (Th1) stimulation and increased the percentage of CD4+ T cells expressing CXCR3. Furthermore, supernatants from IRIV stimulated PBMC cultures promoted dendritic cell maturation. Most importantly, IRIV mediated CTL adjuvance required the presence of live CD4+ T cells. Powerful adjuvant effects of IRIV were also observed in the induction of CTL specific for the melanoma associated Melan-A/MART-127–35, HLA-A0201 restricted epitope. Taken together these findings indicate that IRIV are endowed with a high adjuvant capacity for HLA class I restricted CTL induction, largely attributable to their ability to antigenically stimulate CD4+ T cells.