Preclinical development of HIvax: Human survivin highly immunogenic vaccines.

Abstract

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.

• Authors: Peter R Hoffmann, Maddalena Panigada, Elisa Soprana, Frances Terry, Ivo Sah Bandar, Andrea Napolitano, Aaron H Rose, Fukun W Hoffmann, Lishomwa C Ndhlovu, Mahdi Belcaid, Lenny Moise, Anne S De Groot, Michele Carbone, Giovanni Gaudino, Takashi Matsui, Antonio Siccardi, Pietro Bertino
• Journal: Human vaccines & immunotherapeutics (Hum Vaccin Immunother) Vol. 11 Issue 7 Pg. 1585-95 ( 2015) ISSN: 2164-554X [Electronic] United States
• PMID: 26042612 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• BIRC5 protein, human
• Cancer Vaccines
• Immunodominant Epitopes
• Inhibitor of Apoptosis Proteins
• Survivin
• Interferon-gamma
• Granzymes

Topics

• Antibody Formation
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (genetics, immunology)
• Cell Line, Tumor
• Cells, Cultured
• Dendritic Cells (immunology)
• Genetic Vectors
• Granzymes (immunology, metabolism)
• Humans
• Immunization
• Immunodominant Epitopes (genetics, isolation & purification)
• Inhibitor of Apoptosis Proteins (genetics, immunology)
• Interferon-gamma (immunology, metabolism)
• Lymphocyte Activation
• Mesothelioma
• Survivin
• T-Lymphocytes, Cytotoxic (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Transgenes