Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants

From National Research Council Canada

DOIResolve DOI: http://doi.org/10.1080/21645515.2017.1423154
AuthorSearch for: 1 ; Search for: 1 ; Search for: 1 
Name affiliation
  1. National Research Council Canada. Human Health Therapeutics
TypeArticle
Journal titleHuman Vaccines & Immunotherapeutics
ISSN2164-5515
2164-554X
Volume13
Issue12
Pages2772–2779
Subjectadjuvant; adjuvants; archaeosome; delivery; glycolipid; immune modulators; immune response; mice; vaccine; vaccinology
Abstract
Archaeosomes are liposomal vesicles composed of ether glycerolipids unique to the domain of Archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high stability and possess strong adjuvant and immunostimulatory properties making them an attractive vaccine delivery vehicle. Traditionally comprised of total polar lipids (TPL) or semi-synthetic phospho-glycerolipids of ether-linked isoprenoid phytanyl cores with varied glycol- and amino-head groups, archaeosomes can induce robust and long-lasting humoral and cell-mediated immune responses against antigenic cargo and provide protection in murine models of infectious disease and cancer. However, traditional TPL archaeosome formulations are relatively complex comprising several lipid species. Semi-synthetic archaeosomes tested previously contain a combination of several phospho-glycolipids (negative and neutral charged) to produce a stable, uniform-sized liposome formulation. Moreover, they involve many synthetic steps to arrive at the final desired glycolipid composition. Herein, we present a novel adjuvant formulation comprising a sulfated saccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA). SLA individually or mixed with uncharged glyolipid (lactosylarchaeol, LA) constituted efficacious carrier vesicles for entrapped antigens (ovalbumin or melanoma associated tyrosinase-related protein 2 [TRP-2]) and induction of strong cell-mediated responses in mice and protection against subsequent B16 melanoma tumor challenge. Thus, semi-synthetic sulfated glycolipid archaeosomes represent a new class of adjuvants that will potentially ease manufacturing and scale-up, while retaining immunostimulatory activity.
Publication date
PublisherTaylor & Francis
LanguageEnglish
Peer reviewedYes
NPARC number23002773
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