Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant.
Adjuvant
COVID-19 vaccine
Glycopolymers
Polymer-protein conjugates
Polymeric glyco-adjuvant
Subunit vaccine formulation
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
02
06
2021
revised:
20
09
2021
accepted:
27
09
2021
pubmed:
12
10
2021
medline:
4
11
2021
entrez:
11
10
2021
Statut:
ppublish
Résumé
The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires an effective vaccine which elicits a diverse and robust immune response. We have previously shown that vaccines made of a polymeric glyco-adjuvant conjugated to an antigen were effective in triggering such a response in other disease models and hypothesized that the technology could be adapted to create an effective vaccine against SARS-CoV-2. The core of the vaccine platform is the copolymer p(Man-TLR7), composed of monomers with pendant mannose or a toll-like receptor 7 (TLR7) agonist. Thus, p(Man-TLR7) is designed to target relevant antigen-presenting cells (APCs) via mannose-binding receptors and then activate TLR7 upon endocytosis. The p(Man-TLR7) construct is amenable to conjugation to protein antigens such as the Spike protein of SARS-CoV-2, yielding Spike-p(Man-TLR7). Here, we demonstrate Spike-p(Man-TLR7) vaccination elicits robust antigen-specific cellular and humoral responses in mice. In adult and elderly wild-type mice, vaccination with Spike-p(Man-TLR7) generates high and long-lasting titers of anti-Spike IgGs, with neutralizing titers exceeding levels in convalescent human serum. Interestingly, adsorbing Spike-p(Man-TLR7) to the depot-forming adjuvant alum amplified the broadly neutralizing humoral responses to levels matching those in mice vaccinated with formulations based off of clinically-approved adjuvants. Additionally, we observed an increase in germinal center B cells, antigen-specific antibody secreting cells, activated T follicular helper cells, and polyfunctional Th1-cytokine producing CD4
Identifiants
pubmed: 34634664
pii: S0142-9612(21)00516-0
doi: 10.1016/j.biomaterials.2021.121159
pmc: PMC8482845
pii:
doi:
Substances chimiques
Adjuvants, Immunologic
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
121159Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014599
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA219304
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007090
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
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