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

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...

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Autores principales: Soltanpour Gharibdousti, Faezeh, Fazeli Delshad, Banafsheh, Falak, Reza, Shayanfar, Nasrin, Ganjalikhani Hakemi, Mazdak, Andalib, Alireza, Kardar, Gholam Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mashhad University of Medical Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239427/
https://www.ncbi.nlm.nih.gov/pubmed/32489566
http://dx.doi.org/10.22038/ijbms.2020.38508.9141
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author Soltanpour Gharibdousti, Faezeh
Fazeli Delshad, Banafsheh
Falak, Reza
Shayanfar, Nasrin
Ganjalikhani Hakemi, Mazdak
Andalib, Alireza
Kardar, Gholam Ali
author_facet Soltanpour Gharibdousti, Faezeh
Fazeli Delshad, Banafsheh
Falak, Reza
Shayanfar, Nasrin
Ganjalikhani Hakemi, Mazdak
Andalib, Alireza
Kardar, Gholam Ali
author_sort Soltanpour Gharibdousti, Faezeh
collection PubMed
description 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.
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spelling pubmed-72394272020-06-01 Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine Soltanpour Gharibdousti, Faezeh Fazeli Delshad, Banafsheh Falak, Reza Shayanfar, Nasrin Ganjalikhani Hakemi, Mazdak Andalib, Alireza Kardar, Gholam Ali Iran J Basic Med Sci Original Article 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. Mashhad University of Medical Sciences 2020-04 /pmc/articles/PMC7239427/ /pubmed/32489566 http://dx.doi.org/10.22038/ijbms.2020.38508.9141 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Soltanpour Gharibdousti, Faezeh
Fazeli Delshad, Banafsheh
Falak, Reza
Shayanfar, Nasrin
Ganjalikhani Hakemi, Mazdak
Andalib, Alireza
Kardar, Gholam Ali
Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine
title Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine
title_full Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine
title_fullStr Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine
title_full_unstemmed Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine
title_short Induction of humoral immune responses and inhibition of metastasis in mice by a VEGF peptide-based vaccine
title_sort induction of humoral immune responses and inhibition of metastasis in mice by a vegf peptide-based vaccine
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239427/
https://www.ncbi.nlm.nih.gov/pubmed/32489566
http://dx.doi.org/10.22038/ijbms.2020.38508.9141
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