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

VEGF肽疫苗诱导小鼠体液免疫反应并抑制肿瘤转移

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作者:Faezeh Soltanpour Gharibdousti, Banafsheh Fazeli Delshad, Reza Falak, Nasrin Shayanfar, Mazdak Ganjalikhani Hakemi, Alireza Andalib, Gholam Ali Kardar

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.

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.

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