A COVID-19 vaccine candidate based on SARS-CoV-2 spike protein and immune-stimulating complexes.
Continuous process
HEK293 cells
Immune response
Immune-stimulating complexes adjuvant
Neutralizing antibodies
SARS-CoV-2 spike
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
18
12
2022
accepted:
04
04
2023
revised:
21
03
2023
medline:
15
5
2023
pubmed:
24
4
2023
entrez:
24
04
2023
Statut:
ppublish
Résumé
Spike protein from SARS-CoV-2, the etiologic agent of the COVID-19 pandemic disease, constitutes a structural protein that proved to be the main responsible for neutralizing antibody production. Thus, its sequence is highly considered for the design of candidate vaccines. Animal cell culture represents the best option for the production of subunit vaccines based on recombinant proteins since they introduce post-translational modifications that are important to mimic the natural antigenic epitopes. Particularly, the human cell line HEK293T has been explored and used for the production of biotherapeutics since the products derived from them present human-like post-translational modifications that are important for the protein's activity and immunogenicity. The aim of this study was to produce and characterize a potential vaccine for COVID-19 based on the spike ectodomain (S-ED) of SARS-CoV-2 and two different adjuvants: aluminum hydroxide (AH) and immune-stimulating complexes (ISCOMs). The S-ED was produced in sHEK293T cells using a 1-L stirred tank bioreactor operated in perfusion mode and purified. S-ED characterization revealed the expected size and morphology. High N-glycan content was confirmed. S-ED-specific binding with the hACE2 (human angiotensin-converting enzyme 2) receptor was verified. The immunogenicity of S-ED was evaluated using AH and ISCOMs. Both formulations demonstrated the presence of anti-RBD antibodies in the plasma of immunized mice, being significantly higher for the latter adjuvant. Also, higher levels of IFN-γ and IL-4 were detected after the ex vivo immune stimulation of spleen-derived MNCs from ISCOMs immunized mice. Further analysis confirmed that S-ED/ISCOMs elicit neutralizing antibodies against SARS-CoV-2. KEY POINTS: Trimeric SARS-CoV-2 S-ED was produced in stable recombinant sHEK cells in serum-free medium. A novel S-ED vaccine formulation induced potent humoral and cellular immunity. S-ED formulated with ISCOMs adjuvant elicited a highly neutralizing antibody titer.
Identifiants
pubmed: 37093307
doi: 10.1007/s00253-023-12520-5
pii: 10.1007/s00253-023-12520-5
pmc: PMC10124706
doi:
Substances chimiques
COVID-19 Vaccines
0
spike protein, SARS-CoV-2
0
Spike Glycoprotein, Coronavirus
0
Antigen-Antibody Complex
0
ISCOMs
0
Antibodies, Viral
0
Antibodies, Neutralizing
0
Adjuvants, Immunologic
0
Aluminum Hydroxide
5QB0T2IUN0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3429-3441Subventions
Organisme : Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación
ID : IP-COVID-19-224
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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