Synthetic archaeosome vaccines containing triglycosylarchaeols can provide additive and long-lasting immune responses that are enhanced by archaetidylserine

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DOIResolve DOI: http://doi.org/10.1155/2012/513231
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TypeArticle
Journal titleArchaea
ISSN1472-3646
Volume2012
Article number513231
SubjectArchaea; Halobacterium salinarum; Mus; antibody; archaeol lipid; cancer vaccine; glycerol ether; glycolipid; immunological adjuvant; tumor antigen; animal; article; blood; C57BL mouse; CD4+ T lymphocyte; CD8+ T lymphocyte; chemistry; Halobacterium salinarum; immunology; isolation and purification; mouse; neoplasm; pathology; Adjuvants, Immunologic; Animals; Antibodies; Antigens, Neoplasm; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Glyceryl Ethers; Glycolipids; Halobacterium salinarum; Mice; Mice, Inbred C57BL; Neoplasms
AbstractThe relation between archaeal lipid structures and their activity as adjuvants may be defined and explored by synthesizing novel head groups covalently linked to archaeol (2,3-diphytanyl-sn-glycerol). Saturated archaeol, that is suitably stable as a precursor for chemical synthesis, was obtained in high yield from Halobacterium salinarum. Archaeosomes consisting of the various combinations of synthesized lipids, with antigen entrapped, were used to immunize mice and subsequently determine CD8+ and CD4+-T cell immune responses. Addition of 45 mol of the glycolipids gentiotriosylarchaeol, mannotriosylarchaeol or maltotriosylarchaeol to an archaetidylglycerophosphate-O-methyl archaeosome, significantly enhanced the CD8+ T cell response to antigen, but diminished the antibody titres in peripheral blood. Archaeosomes consisting of all three triglycosyl archaeols combined with archaetidylglycerophosphate-O-methyl (15/15/15/55 mol) resulted in approximately additive CD8+ T cell responses and also an antibody response not significantly different from the archaetidylglycerophosphate-O- methyl alone. Synthetic archaetidylserine played a role to further enhance the CD8+ T cell response where the optimum content was 2030 mol. Vaccines giving best protection against solid tumor growth corresponded to the archaeosome adjuvant composition that gave highest immune activity in immunized mice. © 2012 G. Dennis Sprott et al.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269257
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Record identifiere74241ce-40c2-42f1-827f-d61287ebc165
Record created2013-12-12
Record modified2016-05-09
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