Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine

Soltanpour Gharibdousti, Faezeh and Fazeli Delshad, Banafsheh and Falak, Reza and Shayanfar, Nasrin and Ganjalikhani Hakemi, Mazdak and Andalib, Alireza and Kardar, Gholamali (2020) Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine. Iranian Journal of Basic Medical Sciences, 23 (4). pp. 507-514.

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Abstract

Objective(s): Blocking of vascular endothelial growth factor (VEGF) plays a pivotal role in inhibition of metastasis and is a target for development of anti-angiogenic agents. In this study, a peptide-based vaccine was designed and its potential for induction of humoral immune responses, generation of neutralizing antibodies, inhibition of tumor growth and metastasis was determined.Materials and Methods: With online bioinformatics tools, a fragment of the VEGF-A was selected for a peptide-based vaccine. To enhance its antigenicity, the peptide was conjugated with Keyhole limpet hemocyanin and used to immunize mice. Then, the polyclonal anti-VEGF antibody titer was measured and its effect on proliferation of HUVEC cell line was investigated by MTT assay. Finally, we checked the effect of the peptide on tumor growth, metastasis, and survival rates in a mouse model of cancer.Results: The bioinformatics analysis of the selected region confirmed dis-similarity of the peptide with any other human protein and its acceptable antigenicity to stimulate a tumor-specific humoral response. Anti-VEGF antibody titers were significantly greater in vaccinated mice than in controls. IgG antibody from mice immunized with recombinant VEGF-A inhibited HUVEC proliferation (P<0.0001). Tumors in vaccinated mice were significantly smaller than those in controls. Moreover, metastasis was reduced and survival rates increased in the vaccinated group.Conclusion: Production of high-titer antibody against the peptide vaccine indicated that the peptide has the potency to be used as a peptide-based vaccine for humoral inhibition of tumor growth and metastasis. The efficacy of the peptide should be further tested in primate models.

Item Type: Article
Uncontrolled Keywords: Angiogenesis,Immunoinformatics,Metastasis,Peptide based vaccine,VEGF
Subjects: QU Biochemistry
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 24 Jun 2020 05:09
Last Modified: 24 Jun 2020 05:09
URI: http://eprints.mums.ac.ir/id/eprint/18044

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