Archaeosome vaccine adjuvants induce strong humoral, cell-mediated, and memory responses: Comparison to conventional liposomes and alum

Ether glycerolipids extracted from various archaeobacteria were formulated into liposomes (archaeosomes) possessing strong adjuvant properties. Mice o f varying genetic backgrounds, immunized by different parenteral routes wit h bovine serum albumin (BSA) entrapped in archaeosomes (similar to 200-nm v esicles), demonstrated markedly enhanced serum anti-ESA antibody titers. Th ese titers were often comparable to those achieved with Freund's adjuvant a nd considerably more than those with alum or conventional liposomes (phosph atidylcholine-phosphatidylglycerol-cholesterol, 1.8:0.2:1.5 molar ratio). F urthermore, antigen-specific immunoglobulin G1 (IgG1), IgG2a, and IgG2b iso type antibodies were all induced. Association of BSA with the lipid vesicle s was required for induction of a strong response, and >80% of the protein was internalized within most archaeosome types, suggesting efficient releas e of antigen in vivo. Encapsulation of ovalbumin and hen egg lysozyme withi n archaeosomes showed similar immune responses, Antigen-archaeosome immuniz ations also induced a strong cell-mediated immune response: antigen-depende nt proliferation and substantial production of cytokines gamma interferon ( Th1) and interleukin-4 (IL-4) (Th2) by spleen cells in vitro. In contrast, conventional liposomes induced little cell-mediated immunity, whereas alum stimulated only an IL-4 response. In contrast to alum and Freund's adjuvant , archaeosomes composed of Thermoplasma acidophilum lipids evoked a dramati c memory antibody response to the encapsulated protein (at similar to 300 d ays) after only two initial immunizations (days 0 and 14). This correlated with increased antigen-specific cell cycling of CD4(+) T cells: increase in synthetic (S) and mitotic (G(2)/M) and decrease in resting (G(1)) phases. Thus, archaeosomes may be potent vaccine carriers capable of facilitating s trong primary and memory humoral, and cell-mediated immune responses to the entrapped antigen.