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Exploring yeast glucans for vaccine enhancement: sustainable strategies for overcoming adjuvant challenges in a SARS-CoV-2 model

dc.contributor.authorAzevedo-Silva, João
dc.contributor.authorAmorim, Manuela
dc.contributor.authorTavares-Valente, Diana
dc.contributor.authorSousa, Pedro
dc.contributor.authorMohamath, Randolph
dc.contributor.authorVoigt, Emily A.
dc.contributor.authorGuderian, Jeffrey A.
dc.contributor.authorKinsey, Robert
dc.contributor.authorViana, Sofia
dc.contributor.authorReis, Flávio
dc.contributor.authorPintado, Manuela E.
dc.contributor.authorPaddon, Christopher J.
dc.contributor.authorFox, Christopher B.
dc.contributor.authorFernandes, João C.
dc.date.accessioned2024-10-29T18:08:23Z
dc.date.available2024-10-29T18:08:23Z
dc.date.issued2024-12-01
dc.description.abstractVaccine adjuvants are important for enhancing vaccine efficacy, and although aluminium salts (Alum) are the most used, their limited ability to induce specific immune responses has spurred the search for new adjuvants. However, many adjuvants fail during product development due to manufacturability, supply, stability, or safety concerns. This work hypothesizes that protein-free yeast glucans can be used as vaccine adjuvants due to their known immunostimulatory activity and high abundancy. Thus, high molecular weight glucans with over 99% purity, comprising 64–70% β-glucans and 29–35% α-glucans, were extracted from a wild-type yeast and an engineered yeast to produce a steviol glycoside. These glucans underwent carboxymethylation to enhance solubility. Both water-dispersible and particulate glucans were evaluated as adjuvants, either alone or in combination with Alum or squalene stable emulsion (SE), for a SARS-CoV-2 vaccine. The study demonstrated that glucans triggered a robust immune response and enhanced the effects of Alum and SE when used in combination, both in vitro and in vivo. Water-dispersible glucans combined with Alum, and particulate glucans combined with SE, increased the production of specific antibodies against SARS-CoV-2 spike protein and enhanced serum neutralization titers against SARS-CoV-2 pseudovirus. Furthermore, the results indicated that larger molecular weight glucans from engineered yeast exhibited stronger immunogenic activity in comparison to wild-type yeast glucans. In conclusion, appropriately formulated glucans have the potential to be scalable, low-cost vaccine adjuvants, potentially overcoming the limitations of current adjuvants.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.ejpb.2024.114538pt_PT
dc.identifier.eid85207936536
dc.identifier.issn0939-6411
dc.identifier.pmid39461571
dc.identifier.urihttp://hdl.handle.net/10400.14/47070
dc.identifier.wos001349827100001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectGlucanspt_PT
dc.subjectAdjuvantspt_PT
dc.subjectAluminium saltspt_PT
dc.subjectSqualenept_PT
dc.subjectSARS-CoV-2pt_PT
dc.subjectSaccharomyces cerevisiaept_PT
dc.titleExploring yeast glucans for vaccine enhancement: sustainable strategies for overcoming adjuvant challenges in a SARS-CoV-2 modelpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleEuropean Journal of Pharmaceutics and Biopharmaceuticspt_PT
oaire.citation.volume205
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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