SARS-CoV-2 Protein Nanoparticle Vaccines Formed In Situ From Lyophilized Lipids
© 2023 Wiley-VCH GmbH..
The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) glycoprotein is an appealing immunogen, but associated vaccine approaches must overcome the hapten-like nature of the compact protein and adapt to emerging variants with evolving RBD sequences. Here, a vaccine manufacturing methodology is proposed comprising a sterile-filtered freeze-dried lipid cake formulation that can be reconstituted with liquid proteins to instantaneously form liposome-displayed protein nanoparticles. Mannitol is used as a bulking agent and a small amount of Tween-80 surfactant is required to achieve reconstituted submicron particles that do not precipitate prior to usage. The lipid particles include an E. coli-derived monophosphoryl lipid A (EcML) for immunogenicity, and cobalt porphyrin-phospholipid (CoPoP) for antigen display. Reconstitution of the lipid cake with aqueous protein results in rapid conversion of the RBD into intact liposome-bound format prior to injection. Protein particles can readily be formed with sequent-divergent RBD proteins derived from the ancestral or Omicron strains. Immunization of mice elicits antibodies that neutralize respective viral strains. When K18-hACE2 transgenic mice are immunized and challenged with ancestral SARS-CoV-2 or the Omicron BA.5 variant, both liquid liposomes displaying the RBD and rapid reconstituted particles protect mice from infection, as measured by the viral load in the lungs and nasal turbinates.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Small (Weinheim an der Bergstrasse, Germany) - 20(2024), 9 vom: 01. März, Seite e2304534 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jiao, Yang [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 Vaccines |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/smll.202304534 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) glycoprotein is an appealing immunogen, but associated vaccine approaches must overcome the hapten-like nature of the compact protein and adapt to emerging variants with evolving RBD sequences. Here, a vaccine manufacturing methodology is proposed comprising a sterile-filtered freeze-dried lipid cake formulation that can be reconstituted with liquid proteins to instantaneously form liposome-displayed protein nanoparticles. Mannitol is used as a bulking agent and a small amount of Tween-80 surfactant is required to achieve reconstituted submicron particles that do not precipitate prior to usage. The lipid particles include an E. coli-derived monophosphoryl lipid A (EcML) for immunogenicity, and cobalt porphyrin-phospholipid (CoPoP) for antigen display. Reconstitution of the lipid cake with aqueous protein results in rapid conversion of the RBD into intact liposome-bound format prior to injection. Protein particles can readily be formed with sequent-divergent RBD proteins derived from the ancestral or Omicron strains. Immunization of mice elicits antibodies that neutralize respective viral strains. When K18-hACE2 transgenic mice are immunized and challenged with ancestral SARS-CoV-2 or the Omicron BA.5 variant, both liquid liposomes displaying the RBD and rapid reconstituted particles protect mice from infection, as measured by the viral load in the lungs and nasal turbinates | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Huang, Wei-Chiao |e verfasserin |4 aut | |
| 700 | 1 | |a Chiem, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yiting |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Jingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chothe, Shubhada K |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Shiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Mabrouk, Moustafa T |e verfasserin |4 aut | |
| 700 | 1 | |a Ortega, Joaquin |e verfasserin |4 aut | |
| 700 | 1 | |a Kuchipudi, Suresh V |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez-Sobrido, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Lovell, Jonathan F |e verfasserin |4 aut | |
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