Date of Original Version
Our previous work involved the development of a recombinant fowlpox virus encoding survivin (FP-surv) vaccine that was evaluated for efficacy in mesothelioma mouse models. Results showed that FP-surv vaccination generated significant immune responses, which led to delayed tumor growth and improved animal survival. We have extended those previous findings in the current study, which involves the pre-clinical development of an optimized version of FP-surv designed for human immunization (HIvax). Survivin-derived peptides for the most common haplotypes in the human population were identified and their immunogenicity confirmed in co-culture experiments using dendritic cells and T cells isolated from healthy donors. Peptides confirmed to induce CD8(+) and CD4(+) T cells activation in humans were then included in 2 transgenes optimized for presentation of processed peptides on MHC-I (HIvax1) and MHC-II (HIvax2). Fowlpox vectors expressing the HIvax transgenes were then generated and their efficacy was evaluated with subsequent co-culture experiments to measure interferon-γ and granzyme B secretion. In these experiments, both antigen specific CD4(+) and CD8(+) T cells were activated by HIvax vaccines with resultant cytotoxic activity against survivin-overexpressing mesothelioma cancer cells. These results provide a rationale for clinical testing of HIvax1 and HIvax2 vaccines in patients with survivin-expressing cancers.
Hoffmann, P. R, Panigada, M., Soprana, E., Terry, F., Bandar, I. S., Napolitano, A., Rose, A. H., Hoffmann, F. W., Ndhlovu, L. C., Belcaid, M., Moise, L., De Groot, A. S., Carbone, M., Gaudino, G., Matsui, T., Siccardi, A., & Bertino, P. (2015). Preclinical development of HIvax: human survivin Highly Immunogenic vaccines. Human Vaccines & Immunotherapeutics, 11(7), 1585-1595.