SARS-CoV-2 Protein Nanoparticle Vaccines Formed In Situ From Lyophilized Lipids.
SARS-CoV-2
lipids
liposomes
lyophilization
vaccines
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
17 Oct 2023
17 Oct 2023
Historique:
revised:
05
10
2023
received:
14
07
2023
medline:
18
10
2023
pubmed:
18
10
2023
entrez:
18
10
2023
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 37849036
doi: 10.1002/smll.202304534
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2304534Subventions
Organisme : NIH HHS
ID : 1R43AI165089
Pays : United States
Organisme : NIH HHS
ID : 1R01AI161363
Pays : United States
Organisme : NIH HHS
ID : 1R01AI161175
Pays : United States
Organisme : NIH HHS
ID : R21AI173816
Pays : United States
Organisme : NIH HHS
ID : R01AI145332
Pays : United States
Organisme : NIH HHS
ID : R01AI142985
Pays : United States
Organisme : NIH HHS
ID : 75N95022P00510
Pays : United States
Informations de copyright
© 2023 Wiley-VCH GmbH.
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