Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2
First-generation vaccines against SARS-CoV-2 do not provide adequate immune protection. Therefore, we engineered a divalent gene construct combining the receptor-binding domain (RBD) of the spike protein and the immunodominant region of the viral nucleocapsid. This fusion protein was produced in eit...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/4/516 |
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| author | Zsofia Hevesi Daniela Anna Gerges Sebastian Kapps Raimundo Freire Sophie Schmidt Daniela D. Pollak Klaus Schmetterer Tobias Frey Rita Lang Wolfgang Winnicki Alice Schmidt Tibor Harkany Ludwig Wagner |
| author_facet | Zsofia Hevesi Daniela Anna Gerges Sebastian Kapps Raimundo Freire Sophie Schmidt Daniela D. Pollak Klaus Schmetterer Tobias Frey Rita Lang Wolfgang Winnicki Alice Schmidt Tibor Harkany Ludwig Wagner |
| author_sort | Zsofia Hevesi |
| collection | DOAJ |
| description | First-generation vaccines against SARS-CoV-2 do not provide adequate immune protection. Therefore, we engineered a divalent gene construct combining the receptor-binding domain (RBD) of the spike protein and the immunodominant region of the viral nucleocapsid. This fusion protein was produced in either <i>E. coli</i> or a recombinant baculovirus system. Subsequently, the fusion protein was mixed with adjuvant and administered to mice in a prime-booster mode. Mice (72%) produced an IgG response against both proteins (titer: 10<sup>−4</sup>–10<sup>−5</sup>) 14 days after the first booster injection, which was increased to 100% by a second booster. Comparable IgG responses were detected against the delta, gamma and omicron variants of the RBD region. Durability testing revealed IgGs beyond 90 days. In addition, cytolytic effector cell molecules were increased in lymphocytes isolated from peripheral blood. Ex vivo stimulation of T cells by nucleocapsid and RBD peptides showed antigen-specific upregulation of CD44 among the CD4<sup>+</sup> and CD8<sup>+</sup> T cells of vaccinated mice. No side effect was documented in the central nervous system. Cumulatively, these data represent a proof-of-principle approach alternative to existing mRNA vaccination strategies. |
| first_indexed | 2024-03-09T10:28:08Z |
| format | Article |
| id | doaj.art-62465a1d4a0e4389901a23e8bb732461 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T10:28:08Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-62465a1d4a0e4389901a23e8bb7324612023-12-01T21:30:19ZengMDPI AGVaccines2076-393X2022-03-0110451610.3390/vaccines10040516Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2Zsofia Hevesi0Daniela Anna Gerges1Sebastian Kapps2Raimundo Freire3Sophie Schmidt4Daniela D. Pollak5Klaus Schmetterer6Tobias Frey7Rita Lang8Wolfgang Winnicki9Alice Schmidt10Tibor Harkany11Ludwig Wagner12Center for Brain Research, Department of Molecular Neurosciences, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, AustriaUnidad de Investigacion, Hospital Universitario de Canarias-FIISC, 38320 La Laguna, SpainDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, AustriaCenter for Physiology and Pharmacology, Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, AustriaDivision of Endocrinology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, AustriaCenter for Brain Research, Department of Molecular Neurosciences, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, AustriaFirst-generation vaccines against SARS-CoV-2 do not provide adequate immune protection. Therefore, we engineered a divalent gene construct combining the receptor-binding domain (RBD) of the spike protein and the immunodominant region of the viral nucleocapsid. This fusion protein was produced in either <i>E. coli</i> or a recombinant baculovirus system. Subsequently, the fusion protein was mixed with adjuvant and administered to mice in a prime-booster mode. Mice (72%) produced an IgG response against both proteins (titer: 10<sup>−4</sup>–10<sup>−5</sup>) 14 days after the first booster injection, which was increased to 100% by a second booster. Comparable IgG responses were detected against the delta, gamma and omicron variants of the RBD region. Durability testing revealed IgGs beyond 90 days. In addition, cytolytic effector cell molecules were increased in lymphocytes isolated from peripheral blood. Ex vivo stimulation of T cells by nucleocapsid and RBD peptides showed antigen-specific upregulation of CD44 among the CD4<sup>+</sup> and CD8<sup>+</sup> T cells of vaccinated mice. No side effect was documented in the central nervous system. Cumulatively, these data represent a proof-of-principle approach alternative to existing mRNA vaccination strategies.https://www.mdpi.com/2076-393X/10/4/516receptor-binding domainnucleocapsidbivalent vaccineneuroinflammation |
| spellingShingle | Zsofia Hevesi Daniela Anna Gerges Sebastian Kapps Raimundo Freire Sophie Schmidt Daniela D. Pollak Klaus Schmetterer Tobias Frey Rita Lang Wolfgang Winnicki Alice Schmidt Tibor Harkany Ludwig Wagner Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2 Vaccines receptor-binding domain nucleocapsid bivalent vaccine neuroinflammation |
| title | Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2 |
| title_full | Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2 |
| title_fullStr | Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2 |
| title_full_unstemmed | Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2 |
| title_short | Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2 |
| title_sort | preclinical establishment of a divalent vaccine against sars cov 2 |
| topic | receptor-binding domain nucleocapsid bivalent vaccine neuroinflammation |
| url | https://www.mdpi.com/2076-393X/10/4/516 |
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