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Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies
OBJECTIVE(S): Development of new antibodies with broad activity would provide anti-influenza prophylaxis and treatment. Human single-chain variable fragments (scFvs) are considered effective agents against viruses. In this study specific human scFvs against highly conserved epitopes in the hemagglut...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mashhad University of Medical Sciences
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894632/ https://www.ncbi.nlm.nih.gov/pubmed/33643565 http://dx.doi.org/10.22038/ijbms.2020.43508.10219 |
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author | Alizadeh, Samaneh Moazen, Setareh Faraji, Seyed Nooreddin Moattari, Afagh Nejatollahi, Foroogh |
author_facet | Alizadeh, Samaneh Moazen, Setareh Faraji, Seyed Nooreddin Moattari, Afagh Nejatollahi, Foroogh |
author_sort | Alizadeh, Samaneh |
collection | PubMed |
description | OBJECTIVE(S): Development of new antibodies with broad activity would provide anti-influenza prophylaxis and treatment. Human single-chain variable fragments (scFvs) are considered effective agents against viruses. In this study specific human scFvs against highly conserved epitopes in the hemagglutinin (HA) of influenza A viruses were selected and their neutralizing activity was evaluated. MATERIALS AND METHODS: Bioinformatic methods were used to evaluate HA epitopes. The panning process selected specific clones from a scFv library. PCR and DNA fingerprinting differentiated the common patterns. Soluble forms of scFvs were produced and evaluated using Western blot analysis. The neutralizing effects of anti-HA scFvs were assessed by microneutralization assay using MDCK cells. Real-time PCR was done to determine the exact copy number of the virus following neutralization. RESULTS: Bioinformatic evaluation confirmed the antigenicity and accessibility of the epitopes. Four specific anti-HA scFvs, scFvs I, II, I’, and II’ were selected. The scFvs neutralized 2009 H1N1 pandemic and 83.34%, 79.17%, 75%, and 62.5% reduction in the virus titers were obtained following treatments with scFv-II′, I, I′, and II, respectively. Real-time PCR demonstrated 98.6%, 95.7%, 95.26%, and 91.19% reductions in virus numbers following neutralization with scFv-II′, I, I′, and II, respectively. CONCLUSION: Anti-HA scFvs selected against highly conserved HA of influenza A virus with high neutralizing effects, offer novel human antibodies for prophylaxis and treatment of a wide range of influenza viruses including different subtypes of H1N1, H3N2, and H5N1 influenza A virus. The antibodies have the potential to be used for universal therapy. |
format | Online Article Text |
id | pubmed-7894632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Mashhad University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-78946322021-02-26 Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies Alizadeh, Samaneh Moazen, Setareh Faraji, Seyed Nooreddin Moattari, Afagh Nejatollahi, Foroogh Iran J Basic Med Sci Original Article OBJECTIVE(S): Development of new antibodies with broad activity would provide anti-influenza prophylaxis and treatment. Human single-chain variable fragments (scFvs) are considered effective agents against viruses. In this study specific human scFvs against highly conserved epitopes in the hemagglutinin (HA) of influenza A viruses were selected and their neutralizing activity was evaluated. MATERIALS AND METHODS: Bioinformatic methods were used to evaluate HA epitopes. The panning process selected specific clones from a scFv library. PCR and DNA fingerprinting differentiated the common patterns. Soluble forms of scFvs were produced and evaluated using Western blot analysis. The neutralizing effects of anti-HA scFvs were assessed by microneutralization assay using MDCK cells. Real-time PCR was done to determine the exact copy number of the virus following neutralization. RESULTS: Bioinformatic evaluation confirmed the antigenicity and accessibility of the epitopes. Four specific anti-HA scFvs, scFvs I, II, I’, and II’ were selected. The scFvs neutralized 2009 H1N1 pandemic and 83.34%, 79.17%, 75%, and 62.5% reduction in the virus titers were obtained following treatments with scFv-II′, I, I′, and II, respectively. Real-time PCR demonstrated 98.6%, 95.7%, 95.26%, and 91.19% reductions in virus numbers following neutralization with scFv-II′, I, I′, and II, respectively. CONCLUSION: Anti-HA scFvs selected against highly conserved HA of influenza A virus with high neutralizing effects, offer novel human antibodies for prophylaxis and treatment of a wide range of influenza viruses including different subtypes of H1N1, H3N2, and H5N1 influenza A virus. The antibodies have the potential to be used for universal therapy. Mashhad University of Medical Sciences 2021-01 /pmc/articles/PMC7894632/ /pubmed/33643565 http://dx.doi.org/10.22038/ijbms.2020.43508.10219 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 Alizadeh, Samaneh Moazen, Setareh Faraji, Seyed Nooreddin Moattari, Afagh Nejatollahi, Foroogh Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies |
title | Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies |
title_full | Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies |
title_fullStr | Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies |
title_full_unstemmed | Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies |
title_short | Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies |
title_sort | novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza a viruses: promising agents for universal therapies |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894632/ https://www.ncbi.nlm.nih.gov/pubmed/33643565 http://dx.doi.org/10.22038/ijbms.2020.43508.10219 |
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