Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies

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 i...

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Bibliographic Details
Published in:Iranian journal of basic medical sciences 2021-01, Vol.24 (1), p.17-23
Main Authors: Alizadeh, Samaneh, Moazen, Setareh, Faraji, Seyed Nooreddin, Moattari, Afagh, Nejatollahi, Foroogh
Format: Article
Language:English
Subjects:
Antibodies
Disease prevention
epitope design
hemagglutinin
immunotherapy
Influenza
influenza a virus
neutralizing scfvs
Original
Viruses
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Summary: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. 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. 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. 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.
ISSN:2008-3866
2008-3874
DOI:10.22038/ijbms.2020.43508.10219