Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses
Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vacci...
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Taylor & Francis Group
2021-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2021.1978823 |
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| author | Belén Aparicio Noelia Casares Josune Egea Marta Ruiz Diana Llopiz Sheila Maestro Cristina Olagüe Gloria González-Aseguinolaza Cristian Smerdou Ascensión López-Díaz de Cerio Susana Inogés Felipe Prósper José R. Yuste Francisco Carmona-Torre Gabriel Reina Juan J. Lasarte Pablo Sarobe |
| author_facet | Belén Aparicio Noelia Casares Josune Egea Marta Ruiz Diana Llopiz Sheila Maestro Cristina Olagüe Gloria González-Aseguinolaza Cristian Smerdou Ascensión López-Díaz de Cerio Susana Inogés Felipe Prósper José R. Yuste Francisco Carmona-Torre Gabriel Reina Juan J. Lasarte Pablo Sarobe |
| author_sort | Belén Aparicio |
| collection | DOAJ |
| description | Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund’s adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104–3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80–95% inhibition capacity; p < 0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p < 0.01 and p < 0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19. |
| format | Article |
| id | doaj-art-e9377e08089748589b0baa3afce49ead |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-e9377e08089748589b0baa3afce49ead2025-08-20T02:30:45ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-011011931194610.1080/22221751.2021.1978823Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responsesBelén Aparicio0Noelia Casares1Josune Egea2Marta Ruiz3Diana Llopiz4Sheila Maestro5Cristina Olagüe6Gloria González-Aseguinolaza7Cristian Smerdou8Ascensión López-Díaz de Cerio9Susana Inogés10Felipe Prósper11José R. Yuste12Francisco Carmona-Torre13Gabriel Reina14Juan J. Lasarte15Pablo Sarobe16Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainClínica Universidad de Navarra, Pamplona, SpainClínica Universidad de Navarra, Pamplona, SpainClínica Universidad de Navarra, Pamplona, SpainClínica Universidad de Navarra, Pamplona, SpainClínica Universidad de Navarra, Pamplona, SpainClínica Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainCentro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, SpainIdentification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund’s adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104–3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80–95% inhibition capacity; p < 0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p < 0.01 and p < 0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.https://www.tandfonline.com/doi/10.1080/22221751.2021.1978823SARS-CoV-2peptide vaccineB-cell epitopesneutralizing antibodiesT-cell epitopes |
| spellingShingle | Belén Aparicio Noelia Casares Josune Egea Marta Ruiz Diana Llopiz Sheila Maestro Cristina Olagüe Gloria González-Aseguinolaza Cristian Smerdou Ascensión López-Díaz de Cerio Susana Inogés Felipe Prósper José R. Yuste Francisco Carmona-Torre Gabriel Reina Juan J. Lasarte Pablo Sarobe Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses Emerging Microbes and Infections SARS-CoV-2 peptide vaccine B-cell epitopes neutralizing antibodies T-cell epitopes |
| title | Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses |
| title_full | Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses |
| title_fullStr | Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses |
| title_full_unstemmed | Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses |
| title_short | Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses |
| title_sort | preclinical evaluation of a synthetic peptide vaccine against sars cov 2 inducing multiepitopic and cross reactive humoral neutralizing and cellular cd4 and cd8 responses |
| topic | SARS-CoV-2 peptide vaccine B-cell epitopes neutralizing antibodies T-cell epitopes |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2021.1978823 |
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