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Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations.

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.

journal_name

Hum Vaccin Immunother

journal_title

Human vaccines & immunotherapeutics

authors

Agbayani G,Jia Y,Akache B,Chandan V,Iqbal U,Stark FC,Deschatelets L,Lam E,Hemraz UD,Régnier S,Krishnan L,McCluskie MJ

doi

10.1080/21645515.2020.1788300

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

2183-2195

issue

eissn

2164-5515

issn

2164-554X

journal_volume

pub_type

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Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations.