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Infection and Immunity, January 2000, p. 54-63, Vol. 68, No. 1
0019-9567/0/$04.00+0

Archaeosome Vaccine Adjuvants Induce Strong Humoral, Cell-Mediated, and Memory Responses: Comparison to Conventional Liposomes and Alumdagger

Lakshmi Krishnan,* Chantal J. Dicaire, Girishchandra B. Patel, and G. Dennis Sprott

Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6

Received 1 July 1999/Returned for modification 26 August 1999/Accepted 19 October 1999

Ether glycerolipids extracted from various archaeobacteria were formulated into liposomes (archaeosomes) possessing strong adjuvant properties. Mice of varying genetic backgrounds, immunized by different parenteral routes with bovine serum albumin (BSA) entrapped in archaeosomes (~200-nm vesicles), demonstrated markedly enhanced serum anti-BSA antibody titers. These titers were often comparable to those achieved with Freund's adjuvant and considerably more than those with alum or conventional liposomes (phosphatidylcholine-phosphatidylglycerol-cholesterol, 1.8:0.2:1.5 molar ratio). Furthermore, antigen-specific immunoglobulin G1 (IgG1), IgG2a, and IgG2b isotype antibodies were all induced. Association of BSA with the lipid vesicles was required for induction of a strong response, and >80% of the protein was internalized within most archaeosome types, suggesting efficient release of antigen in vivo. Encapsulation of ovalbumin and hen egg lysozyme within archaeosomes showed similar immune responses. Antigen-archaeosome immunizations also induced a strong cell-mediated immune response: antigen-dependent 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 dramatic memory antibody response to the encapsulated protein (at ~300 days) 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 (G2/M) and decrease in resting (G1) phases. Thus, archaeosomes may be potent vaccine carriers capable of facilitating strong primary and memory humoral, and cell-mediated immune responses to the entrapped antigen.

* Corresponding author. Mailing address: Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Dr., Room 3016, Ottawa, Ontario, Canada K1A 0R6. Phone: (613) 991-6371. Fax: (613) 952-9092. E-mail: lakshmi.krishnan{at}nrc.ca.

dagger National Research Council of Canada publication no. 40403.

Infection and Immunity, January 2000, p. 54-63, Vol. 68, No. 1
0019-9567/0/$04.00+0


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