| Download | - View final version: Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations (PDF, 2.0 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1080/21645515.2020.1788300 |
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| Author | Search for: Agbayani, Gerard1; Search for: Jia, Yimei1; Search for: Akache, Bassel1; Search for: Chandan, Vandana1; Search for: Iqbal, Umar1; Search for: Stark, Felicity C.1; Search for: Deschatelets, Lise1; Search for: Lam, Edmond2; Search for: Hemraz, Usha D.2; Search for: Régnier, Sophie2; Search for: Krishnan, Lakshmi1; Search for: McCluskie, Michael J.1ORCID identifier: https://orcid.org/0000-0001-5538-1363 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
- National Research Council of Canada. Aquatic and Crop Resource Development
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| Format | Text, Article |
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| Subject | archaeosome; adjuvant; sulfated lactosyl archaeol; SLA; archaeol; glycolipid; vaccine |
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| Abstract | Archaeosomes are liposomes formulated using total polar lipids (TPLs) or semi-synthetic glycolipids derived from archaea. Conventional archaeosomes with entrapped antigen exhibit robust adjuvant activity as demonstrated by increased antigen-specific humoral and cell-mediated responses and enhanced protective immunity in various murine infection and cancer models. However, antigen entrapment efficiency can vary greatly resulting in antigen loss during formulation and variable antigen:lipid ratios. In order to circumvent this, we recently developed an admixed archaeosome formulation composed of a single semi-synthetic archaeal lipid (SLA, sulfated lactosylarchaeol) which can induce similarly robust adjuvant activity as an encapsulated formulation. Herein, we evaluate and compare the mechanisms involved in the induction of early innate and antigen-specific responses by both admixed (Adm) and encapsulated (Enc) SLA archaeosomes. We demonstrate that both archaeosome formulations result in increased immune cell infiltration, enhanced antigen retention at injection site and increased antigen uptake by antigen-presenting cells and other immune cell types, including neutrophils and monocytes following intramuscular injection to mice using ovalbumin as a model antigen. In vitro studies demonstrate SLA in either formulation is preferentially taken up by macrophages. Although the encapsulated formulation was better able to induce antigen-specific CD8⁺ T cell activation by dendritic cells in vitro, both encapsulated and admixed formulations gave equivalently enhanced protection from tumor challenge when tested in vivo using a B16-OVA melanoma model. Despite some differences in the immunostimulatory profile relative to the SLA (Enc) formulation, SLA (Adm) induces strong in vivo immunogenicity and efficacy, while offering an ease of formulation. |
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| Publication date | 2020-08-05 |
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| Publisher | Taylor & Francis |
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| Language | English |
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| Peer reviewed | Yes |
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| NRC number | NRC-ACRD-PDB051 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | bb2879dc-1c32-46da-b0e6-3f5e272e507e |
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| Record created | 2020-08-11 |
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| Record modified | 2021-10-14 |
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