title: Mucosal and systemic immune responses by intranasal immunization using archaeal lipid-adjuvanted vaccines.
abstract: The utility of archaeal polar lipids as an adjuvant/delivery system for elicitation of antigen-specific mucosal immune responses in intranasally administered vaccines was investigated. Although unilamellar archaeosomes (liposomes made from archaeal polar lipids) with encapsulated ovalbumin (OVA/archaeosomes) induced anti-OVA IgG antibody responses in sera, they failed to induce anti-OVA IgA antibody responses at mucosal sites. However, the addition of CaCl2 to convert OVA/archaeosomes into an archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) vaccine (OVA/AMVAD) consisting of larger, particulate, aggregated structures resulted in an efficacious intranasal (i.n.) vaccine. Intranasal immunization of mice with OVA/AMVAD vaccines prepared from various archaeal polar lipid compositions elicited anti-OVA IgA antibody responses in sera, feces, bile, vaginal and nasal wash samples. The i.n. immunization also induced anti-OVA IgG, IgG1 and IgG2a antibody responses in sera, as well as cytotoxic T lymphocyte responses. The mucosal and systemic immune responses induced by OVA/AMVAD immunization were generally sustained over several months, and were subject to memory boost responses. Thus, polar archaeal lipids appear to be promising for developing a non-replicating mucosal adjuvant and vaccine delivery system.
authors.affiliation: Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada K1A 0R6. girish.patel@nrc-cnrc.gc.ca
authors.forename: Girishchandra B
authors.initials: GB
authors.lastname: Patel
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Amalia
authors.initials: A
authors.lastname: Ponce
authors.forename: Wangxue
authors.initials: W
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D001105:Archaea / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005995:Glyceryl Ethers / Q000494:pharmacology; D019617:Halobacterium salinarum / Q000737:chemistry; D007109:Immunity / Q000187:drug effects*; D018928:Immunity, Mucosal / Q000187:drug effects*; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007156:Immunologic Memory; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013822:Thermoplasma / Q000737:chemistry; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D005995:Glyceryl Ethers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008055:Lipids; D014612:Vaccines; C094418:caldarchaeol; D010047:Ovalbumin