title: Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements.
abstract: BACKGROUND
  It is now emerging that for vaccines against a range of diseases including influenza, malaria and HIV, the induction of a humoral response is insufficient and a substantial complementary cell-mediated immune response is necessary for adequate protection. Furthermore, for some diseases such as tuberculosis, a cellular response seems to be the sole effector mechanism required for protection. The development of new adjuvants capable of inducing highly complex immune responses with strong antigen-specific T-cell responses in addition to antibodies is therefore urgently needed.
  
  
  RESULTS
  Herein, we describe a cationic adjuvant formulation (CAF01) consisting of DDA as a delivery vehicle and synthetic mycobacterial cordfactor as immunomodulator. CAF01 primes strong and complex immune responses and using ovalbumin as a model vaccine antigen in mice, antigen specific cell-mediated- and humoral responses were obtained at a level clearly above a range of currently used adjuvants (Aluminium, monophosphoryl lipid A, CFA/IFA, Montanide). This response occurs through Toll-like receptor 2, 3, 4 and 7-independent pathways whereas the response is partly reduced in MyD88-deficient mice. In three animal models of diseases with markedly different immunological requirement; Mycobacterium tuberculosis (cell-mediated), Chlamydia trachomatis (cell-mediated/humoral) and malaria (humoral) immunization with CAF01-based vaccines elicited significant protective immunity against challenge.
  
  
  CONCLUSIONS
  CAF01 is potentially a suitable adjuvant for a wide range of diseases including targets requiring both CMI and humoral immune responses for protection.
authors.affiliation: Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. eag@ssi.dk
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.forename: Ida
authors.initials: I
authors.lastname: Rosenkrands
authors.forename: Jon
authors.initials: J
authors.lastname: Hansen
authors.forename: Karima
authors.initials: K
authors.lastname: Brahimi
authors.forename: Brian S
authors.initials: BS
authors.lastname: Vandahl
authors.forename: Claus
authors.initials: C
authors.lastname: Aagaard
authors.forename: Kerstin
authors.initials: K
authors.lastname: Werninghaus
authors.forename: Carsten
authors.initials: C
authors.lastname: Kirschning
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
authors.forename: Frank
authors.initials: F
authors.lastname: Follmann
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D002412:Cations; D002692:Chlamydia trachomatis / Q000378:metabolism; D005260:Female; D006017:Glycolipids / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000276:immunology*; D008288:Malaria / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D010967:Plasmodium yoelii / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D002412:Cations; D006017:Glycolipids; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D014612:Vaccines; C507803:trehalose 6,6'-dibehenate; C015831:dimethyldioctadecylammonium
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