title: 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.affiliation: a Department of Cell and Molecular Biology; John A. Burns School of Medicine ; University of Hawai'i ; Honolulu , HI , USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hoffmann
authors.forename: Maddalena
authors.initials: M
authors.lastname: Panigada
authors.forename: Elisa
authors.initials: E
authors.lastname: Soprana
authors.forename: Frances
authors.initials: F
authors.lastname: Terry
authors.forename: Ivo Sah
authors.initials: IS
authors.lastname: Bandar
authors.forename: Andrea
authors.initials: A
authors.lastname: Napolitano
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Rose
authors.forename: Fukun W
authors.initials: FW
authors.lastname: Hoffmann
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.forename: Mahdi
authors.initials: M
authors.lastname: Belcaid
authors.forename: Lenny
authors.initials: L
authors.lastname: Moise
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudino
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsui
authors.forename: Antonio
authors.initials: A
authors.lastname: Siccardi
authors.forename: Pietro
authors.initials: P
authors.lastname: Bertino
mesh_terms: D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005822:Genetic Vectors; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000235:genetics / Q000302:isolation & purification; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008654:Mesothelioma; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019076:Transgenes
chemical_list: C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D007371:Interferon-gamma; D053804:Granzymes
keywords: EpiMatrix; T-Lymphocytes; cancer vaccines; fowlpox; immunodominant epitopes; mesothelioma; tregitopes