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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-? 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.

SUBMITTER: Hoffmann PR

PROVIDER: S-EPMC4514257 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Preclinical development of HIvax: Human survivin highly immunogenic vaccines.

Hoffmann Peter R PR Panigada Maddalena M Soprana Elisa E Terry Frances F Bandar Ivo Sah IS Napolitano Andrea A Rose Aaron H AH Hoffmann Fukun W FW Ndhlovu Lishomwa C LC Belcaid Mahdi M Moise Lenny L De Groot Anne S AS Carbone Michele M Gaudino Giovanni G Matsui Takashi T Siccardi Antonio A Bertino Pietro P

Human vaccines & immunotherapeutics 20150101 7

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). S ...[more]

PMID: 26042612

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Preclinical development of HIvax: Human survivin highly immunogenic vaccines.

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Preclinical development of HIvax: Human survivin highly immunogenic vaccines.

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