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...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2021-01-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_16981_0b1d84e25b012b950f5be4fb330dc288.pdf |
| _version_ | 1818886146190475264 |
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| author | Samaneh Alizadeh Setareh Moazen Seyed Nooreddin Faraji Afagh Moattari Foroogh Nejatollahi |
| author_facet | Samaneh Alizadeh Setareh Moazen Seyed Nooreddin Faraji Afagh Moattari Foroogh Nejatollahi |
| author_sort | Samaneh Alizadeh |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T16:16:42Z |
| format | Article |
| id | doaj.art-bc91835449994d83b29e366df4abec1d |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-19T16:16:42Z |
| publishDate | 2021-01-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-bc91835449994d83b29e366df4abec1d2022-12-21T20:14:35ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742021-01-01241172310.22038/ijbms.2020.43508.1021916981Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapiesSamaneh Alizadeh0Setareh Moazen1Seyed Nooreddin Faraji2Afagh Moattari3Foroogh Nejatollahi4Recombinant Antibody Laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, IranFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver BC, CanadaRecombinant Antibody Laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, IranRecombinant Antibody Laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, IranObjective(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.https://ijbms.mums.ac.ir/article_16981_0b1d84e25b012b950f5be4fb330dc288.pdfepitope designhemagglutininimmunotherapyinfluenza a virusneutralizing scfvs |
| spellingShingle | Samaneh Alizadeh Setareh Moazen Seyed Nooreddin Faraji Afagh Moattari Foroogh Nejatollahi Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies Iranian Journal of Basic Medical Sciences epitope design hemagglutinin immunotherapy influenza a virus neutralizing scfvs |
| 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 | epitope design hemagglutinin immunotherapy influenza a virus neutralizing scfvs |
| url | https://ijbms.mums.ac.ir/article_16981_0b1d84e25b012b950f5be4fb330dc288.pdf |
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