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Hum Vaccin Immunother. 2015;11(7):1585-95. doi: 10.1080/21645515.2015.1050572.

Preclinical development of HIvax: Human survivin highly immunogenic vaccines.

Author information

1
a Department of Cell and Molecular Biology; John A. Burns School of Medicine ; University of Hawai'i ; Honolulu , HI , USA.

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.

KEYWORDS:

EpiMatrix; T-Lymphocytes; cancer vaccines; fowlpox; immunodominant epitopes; mesothelioma; tregitopes

PMID:
26042612
PMCID:
PMC4514257
DOI:
10.1080/21645515.2015.1050572
[Indexed for MEDLINE]
Free PMC Article

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