LU102016B1 - Vaccines based on an antigen protein fused to a nanostructuring scaffold - Google Patents
Vaccines based on an antigen protein fused to a nanostructuring scaffold Download PDFInfo
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- LU102016B1 LU102016B1 LU102016A LU102016A LU102016B1 LU 102016 B1 LU102016 B1 LU 102016B1 LU 102016 A LU102016 A LU 102016A LU 102016 A LU102016 A LU 102016A LU 102016 B1 LU102016 B1 LU 102016B1
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Claims (18)
1. Polypeptid umfassend eine Polypeptidantigendomäne, die genetisch mittels eines flexiblen Polypeptidlinkers an ein selbst-assemblierendes Polypeptidgerüst fusioniert ist, wobei das selbst-assemblierende Polypeptidgerüst dazu eingerichtet ist einen selbst-assemblierten Nanopartikel zu bilden, umfassend das Polypeptidantigen in einem oligomerisierten Zustand, wobei die Anzahl an Polypeptidantigendomänen in dem selbst-assemblierten Nanopartikel gleich oder größer als sechs ist und wobei das selbst-assemblierende Polypeptidgerüst die folgenden Domänen umfasst: eine Kern-Oligomerisierungsdomäne basierend auf Packen basierend auf hydrophoben Aminosäuren, beta-Faltblatt-bildenden Peptidsegmenten oder Clustern aromatischer Reste umfassend mindestens zwei Phenylalanin-Reste; geladener Loslichkeits- und AbstolBungsverbesserungsreste, bevorzugt umfassend 1-6 Reste derselben Ladung und gegebenenfalls mindestens eine Oligomerisierungsdomäne, die dazu eingerichtet ist Proteinantigenen definierte Oligomere zu bieten, umfassend beispielsweise zwei, drei oder vier Kopien.
2. Polypeptid nach Anspruch 1, wobei das selbst-assemblierende Polypeptidgerüst ausgewählt ist aus einem Foldon-Peptid, bevorzugt nach einer von SEQ ID NOs: 6 (AA 228-256), 14 (AA 112-140), 36 (AA 248-274) und 40 (AA 112-140), einem beta-Annulus Peptid, bevorzugt nach einer von SEQ ID NOs: 2 (AA 26-49), 16 (AA 26-49), 38 (AA 146-169) und 40 (AA 144-167) oder den korrespondierenden homologen Segmenten und/oder einem Gerüst für lôsliche Proteinantigenoligomere, wie ein Gerüst nach einer von SEQ ID NOs: 22 (AA 25- A2), 24 (AA 244-260), 26 (AA 244-260), 28 (AA 244-260), 30 (AA 244-252), 32 (AA 244-267), 34 (AA 1302-1318) und 36 (AA 280-295) oder den korrespondierenden homologen Segmenten und/oder wobei der Linker 0 bis 10 Aminosäurereste umfasst, bevorzugt ausgewählt aus Glycin und Serin.
3. DNA oder RNA Nukleotidsequenz umfassend eine Kodierungssequenz für das Polypeptid nach Anspruch 1 oder Anspruch 2, gegebenenfalls wobei die DNA oder RNA Nukleotidsequenz in einem Plasmid, einer linearen oder zirkulären Nukleinsäure oder innerhalb eines anderen Abgabevektors wie einem Virus integriert ist.
4. Protein umfassend das Polypeptid nach Anspruch 1 oder Anspruch 2.
5. Impfstoff umfassend die Nukleotidsequenz nach Anspruch 3 oder das Protein nach Anspruch 4.
6. Polypeptid nach Anspruch 1 oder 2, wobei die Polypeptidantigendomäne eine Domäne des Spike Proteins von SARS-CoV-2 fusioniert an den N-Terminus des selbst-assemblierenden Polypeptidgerüsts und/oder eine Domäne des Spike 1
Proteins von SARS-CoV-2 fusioniert an den C-Terminus des selbst- assemblierenden Polypeptidgerüsts umfasst, gegebenenfalls wobei das selbst- assemblierende Polypeptidgerüst ein Foldon-Peptid ist und/oder dazu eingerichtet ist einen selbst-assemblierten Nanopartikel, umfassend sechs Kopien der Spike Proteindomäne, zu bilden, bevorzugt wobei das selbst-assemblierende Polypeptidgerüst ein Foldon-Peptid ist und dazu eingerichtet ist einen selbst- assemblierten Nanopartikel, umfassend sechs Kopien der Spike Proteindomäne, zu bilden.
7. Polypeptid nach Anspruch 1 oder Anspruch 2, wobei die Polypeptidantigendomäne eine RBD Domäne des Spike Proteins von SARS-CoV- 2 fusioniert an den N-Terminus des selbst-assemblierenden Polypeptidgerüsts und/oder eine RBD Domäne des Spike Proteins von SARS-CoV-2 fusioniert an den C-Terminus des selbst-assemblierenden Polypeptidgerüsts umfasst, bevorzugt wobei die RBD Domäne unabhängig ausgewählt ist von einer von SEQ ID NOs: 2 (AA 65-263), 4 (AA 227-399), 6 (AA 26-224; 259-458), 8 (AA 225-377), 18 (AA 26-224), 22 (AA 43-241), 24 (AA 44-242), 26 (AA 44-242), 28 (AA 44-242), (AA 44-242), 32 (AA 44-242) und 36 (AA 43-242) oder den korrespondierenden homologen Segmenten, gegebenenfalls wobei das selbst-assemblierende Polypeptidgerüst ein trimerisierendes Peptid ist und/oder dazu eingerichtet ist einen selbst-assemblierten Nanopartikel, umfassend sechs Kopien der RBD Spike Proteindomäne, zu bilden, bevorzugt wobei das selbst-assemblierende | Polypeptidgerüst ein trimerisierendes Peptid ist und dazu eingerichtet ist einen | selbst-assemblierten Nanopartikel, umfassend sechs Kopien der RBD Spike | Proteindomäne, zu bilden. |
8. Polypeptid nach Anspruch 1 oder Anspruch 2, wobei die | Polypeptidantigendomäne eine HRC Domäne des Spike Proteins von SARS-CoV- | 2 fusioniert an den N-Terminus des selbst-assemblierenden Polypeptidgerüsts | und/oder eine HRC Domäne des Spike Proteins von SARS-CoV-2 fusioniert an | den C-Terminus des selbst-assemblierenden Polypeptidgeriists umfasst, | bevorzugt wobei die HRC Domäne unabhängig ausgewählt ist von einer von SEQ | ID NOs: 10 (AA 26-108), 12 (AA 26-108), 14 (AA 26-108; 144-226), 16 (AA 65- | 147), 20 (AA 177-159), 38 (AA 26-108) und 40 (AA 26-108) oder den | korrespondierenden homologen Segmenten, gegebenenfalls wobei das selbst- | assemblierende Polypeptidgerüst ein trimerisierendes Peptid ist und/oder dazu | eingerichtet ist einen selbst-assemblierten Nanopartikel, umfassend sechs Kopien | der HRC Spike Proteindomäne, zu bilden, bevorzugt wobei das selbst- | assemblierende Polypeptidgerüst ein trimerisierendes Peptid ist und dazu | eingerichtet ist einen selbst-assemblierten Nanopartikel, umfassend sechs Kopien | der HRC Spike Proteindoméne, zu bilden. |
9. Polypeptid nach Anspruch 1 oder Anspruch 2, wobei die | Polypeptidantigendomäne eine Domäne des Spike Proteins von SARS-CoV-2 | fusioniert an das selbst-assemblierende Polypeptidgertist umfasst, wobei das | selbst-assemblierende Polypeptidgerüst ein beta-Annulus Peptid nach einer von | SEQ ID NOs: 2 (AA 26-49), 16 (AA 26-49), 38 (AA 146-169) und 40 (AA 144-167) | oder den korrespondierenden homologen Segmenten ist, und gegebenenfalls
LU102016 | dazu eingerichtet ist einen selbst-assemblierten Nanopartikel, umfassend mehr als | sechs Kopien der Spike Proteindomäne, zu bilden. ;
10. Polypeptid nach Anspruch 1 oder Anspruch 2, wobei die | Polypeptidantigendomäne eine RBD Domäne des Spike Proteins von SARS-CoV- ; 2 nach SEQ ID NO: 2 (AA 26-49) oder das korrespondierende homologe Segment | fusioniert an das selbst-assemblierende Polypeptidgerüst umfasst, wobei das | selbst-assemblierende Polypeptidgerüst ein beta-Annulus Peptid nach SEQ ID ; NO: 2 (AA 65- 263) oder das korrespondierende homologe Segment ist, und ; gegebenenfalls dazu eingerichtet ist einen selbst-assemblierten Nanopartikel, | umfassend sechs Kopien der RBD Spike Proteindomäne, zu bilden. |
11. Polypeptid nach Anspruch 1 oder Anspruch 2, wobei die | Polypeptidantigendomäne eine HRC Domäne des Spike Proteins von SARS-CoV- | 2 nach einer von SEQ ID NOs: 16 (AA 65-147), 38 (AA 26-108) und 40 (AA 26- . 108) oder den korrespondierenden homologen Segmenten fusioniert an das | selbst-assemblierende Polypeptidgerlist umfasst, wobei das selbst | assemblierende Polypeptidgerüst ein beta-Annulus Peptid nach einer von SEQ ID ; NOs: 16 (AA 26-49), 38 (AA 146-169) und 40 (AA 144-167) oder den / korrespondierenden homologen Segmenten ist, und gegebenenfalls dazu ; eingerichtet ist einen selbst-assemblierten Nanopartikel, umfassend sechs Kopien | der HRC Spike Proteindomäne, zu bilden. |
12. Impfstoff umfassend ein Protein umfassend ein Polypeptid nach einem der ' Ansprüche 6-11. |
13. Nukleinsäure kodierend für das Polypeptid nach einem der Anspriiche 6-11. :
14. Impfstoff umfassend eine Nukleinsäure nach Anspruch 13 in Form von DNA oder | RNA gegebenenfalls enthalten in einem Vektor zur Abgabe an Zellen oder einen | Organismus. |
15. Impfstoff nach Anspruch 12 oder Anspruch 14 zur Verwendung in einer Therapie, | insbesondere bei der Behandlung und/oder Prävention einer viralen Infektion. |
16. Polypeptid umfassend die RBD oder HRC Domänen des Spike Proteins von SARS-CoV-2 fusioniert an ein selbst-assemblierendes Polypeptidgerüst, wobei das selbst-assemblierende Polypeptidgerlist eine Aequifex aeolicus ; Lumazinsynthase bevorzugt nach einer von SEQ ID NOs: 8 (AA 224-377) und 20 (AA 15-168) oder den korrespondierenden homologen Segmenten ist.
17. Nukleinsäure kodierend für das Polypeptid nach Anspruch 16.
18. Impfstoff umfassend eine Nukleinsäure nach Anspruch 17 in Form von DNA oder RNA gegebenenfalls enthalten in einem Vektor zur Abgabe an Zellen, an einen Organismus. 3
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| PCT/EP2021/073632 WO2022043449A1 (en) | 2020-08-26 | 2021-08-26 | Vaccines based on an antigen protein fused to a nanostructuring scaffold |
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| CN121175412A (zh) * | 2023-05-02 | 2025-12-19 | Ａｇｃ株式会社 | 人工病毒衣壳 |
| CN121969386A (zh) | 2023-09-12 | 2026-05-01 | 蒙得维的亚巴斯德研究所 | 用于蜱虫疫苗的通用免疫原性模块和纳米颗粒 |
| WO2025106754A1 (en) | 2023-11-15 | 2025-05-22 | BioNTech SE | Coronavirus vaccine |
| FR3155424A1 (fr) | 2023-11-15 | 2025-05-23 | BioNTech SE | Compositions immunogènes contre le sars-cov-2 |
| WO2026047603A1 (en) | 2024-08-28 | 2026-03-05 | BioNTech SE | Sars-cov-2 immunogenic compositions |
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| WO2005056585A2 (en) * | 2003-12-10 | 2005-06-23 | Agency For Science Technology And Research | Sars coronavirus s proteins and uses thereof |
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