Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope
Vaccination against dengue virus is challenged by the fact that a generic immune response can induce antibody-dependent-enhancement (ADE) in secondary infections. Only some antibodies targeting a quaternary epitope formed by the dimerization of the virus protein E possess sufficient neutralizing cap...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/3/551 |
| _version_ | 1797613194075701248 |
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| author | Monica Poggianella Robert Bernedo Sandra Oloketuyi Ario de Marco |
| author_facet | Monica Poggianella Robert Bernedo Sandra Oloketuyi Ario de Marco |
| author_sort | Monica Poggianella |
| collection | DOAJ |
| description | Vaccination against dengue virus is challenged by the fact that a generic immune response can induce antibody-dependent-enhancement (ADE) in secondary infections. Only some antibodies targeting a quaternary epitope formed by the dimerization of the virus protein E possess sufficient neutralizing capacity. Therefore, the immunization with anti-idiotypic antibodies of neutralizing antibodies might represent a safe vaccination strategy. Starting from a large pre-immune library, we succeeded in isolating a wide set of anti-idiotypic nanobodies characterized by selective and strong binding to the paratope of the neutralizing antibody 1C10. However, the mice immunized with such constructs did not produce effective antibodies, despite at least some of them eliciting an immune response selective for the nanobody variable regions. The results suggest that complex conformational epitopes might be difficult to be recreated by anti-idiotypic structures. The selection process of the anti-idiotypic candidates might be optimized by applying epitope mapping and modeling approaches aimed at identifying the key residues that is necessary to bind to trigger selective immune response. |
| first_indexed | 2024-03-11T06:52:24Z |
| format | Article |
| id | doaj.art-4270fbd6b739473d84220cade5ab0025 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T06:52:24Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-4270fbd6b739473d84220cade5ab00252023-11-17T09:52:53ZengMDPI AGBiomolecules2218-273X2023-03-0113355110.3390/biom13030551Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral EpitopeMonica Poggianella0Robert Bernedo1Sandra Oloketuyi2Ario de Marco3Molecular Immunology Laboratory, International Centre for Genetic Engineering and Biotechnolgy, Padriciano 99, 34149 Trieste, ItalyLaboratory for Environmental and Life Sciences, University of Nova Gorica, 5000 Nova Gorica, SloveniaLaboratory for Environmental and Life Sciences, University of Nova Gorica, 5000 Nova Gorica, SloveniaLaboratory for Environmental and Life Sciences, University of Nova Gorica, 5000 Nova Gorica, SloveniaVaccination against dengue virus is challenged by the fact that a generic immune response can induce antibody-dependent-enhancement (ADE) in secondary infections. Only some antibodies targeting a quaternary epitope formed by the dimerization of the virus protein E possess sufficient neutralizing capacity. Therefore, the immunization with anti-idiotypic antibodies of neutralizing antibodies might represent a safe vaccination strategy. Starting from a large pre-immune library, we succeeded in isolating a wide set of anti-idiotypic nanobodies characterized by selective and strong binding to the paratope of the neutralizing antibody 1C10. However, the mice immunized with such constructs did not produce effective antibodies, despite at least some of them eliciting an immune response selective for the nanobody variable regions. The results suggest that complex conformational epitopes might be difficult to be recreated by anti-idiotypic structures. The selection process of the anti-idiotypic candidates might be optimized by applying epitope mapping and modeling approaches aimed at identifying the key residues that is necessary to bind to trigger selective immune response.https://www.mdpi.com/2218-273X/13/3/551nanobodiesdengueanti-idiotypic antibodiesvaccinationimmune responsepanning |
| spellingShingle | Monica Poggianella Robert Bernedo Sandra Oloketuyi Ario de Marco Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope Biomolecules nanobodies dengue anti-idiotypic antibodies vaccination immune response panning |
| title | Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope |
| title_full | Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope |
| title_fullStr | Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope |
| title_full_unstemmed | Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope |
| title_short | Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope |
| title_sort | nanobodies selectively binding to the idiotype of a dengue virus neutralizing antibody do not necessarily mimic the viral epitope |
| topic | nanobodies dengue anti-idiotypic antibodies vaccination immune response panning |
| url | https://www.mdpi.com/2218-273X/13/3/551 |
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