Augmentation of Human Influenza A Virus-Specific Cytotoxic T Lymphocyte Memory by Influenza Vaccine and Adjuvanted Carriers (ISCOMS)

Abstract

There is a need to improve the ability of subunit vaccines to induce CD8(+) CTL responses in humans, especially for vaccines used to prevent illness by organisms that undergo antigenic variation at their major neutralizing antibody sites, e.g., influenza A viruses and human immunodeficiency virus. Murine models have demonstrated the protective role of cross-reactive CTL against influenza A virus antigenic drift. We tested the ability of an adjuvanted carrier (Iscomatrix) to help human antigen-presenting cells present formalin-killed influenza vaccine to human CD8(+) CTL clones in vitro and in vaccinated humans. The results of a randomized, double-blind, controlled clinical study demonstrate that a single dose of a vaccine formulated into Iscom particles increased influenza A virus-specific CTL memory in 50-60% of recipients, compared to 5% of the recipients of the standard influenza vaccine.

Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

“…The CTL test involved seven days of antigenic stimulation in vitro before testing for CTLs. The present results are in agreement with previous published data (20,21) in demonstrating only minimal increases in CTL responses following administration with inactivated influenza vaccines. This is most likely due to the insensitivity of the 51 Cr-release assay as previously suggested by IFN-γ ELISPOT and peptide-tetramer assays (22).…”

Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX™ vaccine: A phase I study in healthy volunteers

“…Cultures were replenished with fresh medium every 2-3 days and split according to cell density. Cells were harvested on day 7 and assayed for intracellular IFNγ expression against T2 cells pulsed with the stimulating peptide or a HLA-A*0201-restricted Hepatitis B virus (HBV) Core peptide, HBV Core [18][19][20][21][22][23][24][25][26][27] (FLPSDFFPSV) as a negative control. Binding of the appropriate HLA-A*0201/peptide tetramer was measured on the same population.…”

“…10 A range of ISCOMATRIX TM vaccines have now been tested in humans in the setting of cancer and chronic infectious diseases and demonstrated the generation of robust antibody and T cell responses. [25][26][27][28] The core protein is the most highly conserved HCV protein among the different genotypes. Cellular immune responses to core protein have been associated with a positive response to anti-viral treatments 29 and with a milder course of disease.…”

NY-ESO-1 Protein Formulated in ISCOMATRIX Adjuvant Is a Potent Anticancer Vaccine Inducing Both Humoral and CD8+ T-Cell-Mediated Immunity and Protection against NY-ESO-1+ Tumors

“…ϩ CTL responses to several viral and cancer antigens (21)(22)(23). ISCOMATRIX vaccines have a number of potential advantages for use in cancer immunotherapy.…”