Archaeobacterial Ether Lipid Liposomes as Vaccine Adjuvants

Abstract

Archaeosomes are mixed adjuvants capable of promoting strong humoral, cell-mediated (Th1), cytotoxic T-cell–mediated (Th1), and cytotoxic T-cell responses to entrapped protein antigens. The physical association of the protein antigen with the archaeosome seems to be important for the induction of a strong humoral response. The immunization of mice with archaeosome encapsulated bovine serum albumin, ovalbumin (OVA), or lysozyme results in strong cell-mediated immune responses. In addition to major histocompatibility complex (MHC) class II presentation, archaeosomes induce a strong MHC class I presentation of associated protein antigens by antigen presenting cells (APCs), both in vitro and in vivo. The induced cytotoxic T-cell response is CD8+ T-cell dependent, because killing of target cells does not occur on removal of effector CD8+ T cells and is primarily perforin mediated, because killing was not induced in perforin-deficient mice. Adjuvant activity is sufficiently potent to bypass a requirement for CD4+ T-cell help. Comparisons with conventional liposomes and alum were made throughout all these adjuvant activity studies, and the comparisons indicate clearly the superior adjuvant activities of archaeosomes. Archaeosomes enhanced both the recruitment and activation of antigen presenting cells (APC) (dendritic cells and macrophages) to the injection site in mice. The induction of immunological memory can be striking following a primary archaeosome—antigen adjuvanted immune response.