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Interleukin-13 peptide vaccine induces protective humoral immunity in murine asthma models.

ABSTRACT: This study presents a rational design approach to discovery synthetic peptide vaccine candidates from endogenous proteins for chronic non-infectious diseases immunological therapeutics. The approach described the screening of key antigenic amino acid residues of the interleukine-13, which is up-regulated expression in asthma, followed by the development of immunological helper epitope peptides via an integrative computational and experimental method. Notably, this totally synthetic peptide vaccine was capable of stimulating humoral immune responses much stronger than those of parental antigenic peptides by enhancing the efficiency of antigen presentation, and had effective treatment in mouse asthma models. Our approach offers new possibilities to discovery therapeutic peptide vaccine candidates for chronic non-infectious diseases, with highly consolidated in silico and animal disease models for fast iterative screening.

SUBMITTER: Wu F

PROVIDER: S-EPMC5805505 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Interleukin-13 peptide vaccine induces protective humoral immunity in murine asthma models.

Wu Fengbo F Huang Yan Y Zhang Peng P Wang Chunting C Tian Yaomei Y Lu Lian L He Gu G Yang Li L

Oncotarget 20170804 6

This study presents a rational design approach to discovery synthetic peptide vaccine candidates from endogenous proteins for chronic non-infectious diseases immunological therapeutics. The approach described the screening of key antigenic amino acid residues of the interleukine-13, which is up-regulated expression in asthma, followed by the development of immunological helper epitope peptides <i>via</i> an integrative computational and experimental method. Notably, this totally synthetic peptid ...[more]

PMID: 29467919

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Project description:BackgroundDNA vaccines represent an attractive approach for cancer treatment by inducing active T cell and B cell immune responses to tumor antigens. Previous studies have shown that interleukin-13 receptor ?2 chain (IL-13R?2), a tumor-associated antigen is a promising target for cancer immunotherapy as high levels of IL-13R?2 are expressed on a variety of human tumors. To enhance the effectiveness of DNA vaccine, we used extracellular domain of IL-13R?2 (ECD?2) as a protein-boost against murine tumor models.MethodsWe have developed murine models of tumors naturally expressing IL-13R?2 (MCA304 sarcoma, 4T1 breast carcinoma) and D5 melanoma tumors transfected with human IL-13R?2 in syngeneic mice and examined the antitumor activity of DNA vaccine expressing IL-13R?2 gene with or without ECD?2 protein mixed with CpG and IFA adjuvants as a boost vaccine.ResultsMice receiving IL-13R?2 DNA vaccine boosted with ECD?2 protein were superior in exhibiting inhibition of tumor growth, compared to mice receiving DNA vaccine alone, in both prophylactic and therapeutic vaccine settings. In addition, prime-boost vaccination significantly prolonged the survival of mice compared to DNA vaccine alone. Furthermore, ECD?2 booster vaccination increased IFN-? production and CTL activity against tumor expressing IL-13R?2. The immunohistochemical analysis showed the infiltration of CD4 and CD8 positive T cells and IFN-?-induced chemokines (CXCL9 and CXCL10) in regressing tumors of immunized mice. Finally, the prime boost strategy was able to reduce immunosuppressive CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in the spleen and tumor of vaccinated mice.ConclusionThese results suggest that immunization with IL-13R?2 DNA vaccine followed by ECD?2 boost mixed with CpG and IFA adjuvants inhibits tumor growth in T cell dependent manner. Thus our results show an enhancement of efficacy of IL-13R?2 DNA vaccine with ECD?2 protein boost and offers an exciting approach in the development of new DNA vaccine targeting IL-13R?2 for cancer immunotherapy.

Dataset Information

Interleukin-13 peptide vaccine induces protective humoral immunity in murine asthma models.

Publications

Interleukin-13 peptide vaccine induces protective humoral immunity in murine asthma models.

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