title: The cationic lipid, diC14 amidine, extends the adjuvant properties of aluminum salts through a TLR-4- and caspase-1-independent mechanism.
abstract: Adjuvant efficiency is critical for inducing a protective and long-lasting immune response against weak immunogenic antigens. Discovered more than 70 years ago, aluminum salts remain the most widely used adjuvant in human vaccine. Prone to induce a strong humoral response, alum fails to drive a cell-mediated immunity, which is essential to fight against intracellular pathogens. Adjuvant systems that contain more than one component may represent an excellent alternative for completing the lack of T cell immunity associated with the injection of alum-based vaccine. In this work, we demonstrated that the adjuvant effects of alum strongly benefited from combining with a cationic lipid, the diC14 amidine. Indeed, we measured a significant improvement of alum-driven IL-1β release when human macrophages were co-cultured with a mixed suspension of alum and the diC14 amidine. Morphological analysis suggested that diC14 amidine improved the alum uptake by phagocytes. Furthermore, the addition of diC14 amidine to alum efficiently enhanced antigen processing and cross-presentation by antigen presenting cells. The biological relevance of these in vitro data was assessed by measuring the in vivo development of a cytotoxic activity and the enhanced synthesis of antigen-specific immunoglobulins after immunization with alum combined to diC14 amidine. Mechanistically, we demonstrated that diC14 amidine supported the alum adjuvanticity independently of the TLR-4 and caspase-1 agonist activities of the cationic lipid. Based on our findings, we conclude that diC14 amidine works synergistically with alum to achieve higher immune protection after vaccination.
authors.affiliation: Institute for Medical Immunology (IMI), Université libre de Bruxelles (ULB), CP305, Campus Gosselies, Rue Adrienne Bolland 8, 6041 Gosselies, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Wilmar
authors.forename: Caroline
authors.initials: C
authors.lastname: Lonez
authors.forename: Marjorie
authors.initials: M
authors.lastname: Vermeersch
authors.forename: Mathieu
authors.initials: M
authors.lastname: Andrianne
authors.forename: David
authors.initials: D
authors.lastname: Pérez-Morga
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ruysschaert
authors.forename: Michel
authors.initials: M
authors.lastname: Vandenbranden
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.forename: Stéphane T
authors.initials: ST
authors.lastname: Temmerman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage*; D000578:Amidines / Q000008:administration & dosage*; D000818:Animals; D020170:Caspase 1 / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010047:Ovalbumin / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000578:Amidines; D053583:Interleukin-1beta; C089665:N-t-butyl-n'-tetradecyl-3-tetradecylaminopropionamidine; D051197:Toll-Like Receptor 4; D022223:Vaccines, Subunit; C041524:aluminum sulfate; D010047:Ovalbumin; D020170:Caspase 1