Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements.
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.
Agger
Else Marie
EM
Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. eag@ssi.dk
Rosenkrands
Ida
I
Hansen
Jon
J
Brahimi
Karima
K
Vandahl
Brian S
BS
Aagaard
Claus
C
Werninghaus
Kerstin
K
Kirschning
Carsten
C
Lang
Roland
R
Christensen
Dennis
D
Theisen
Michael
M
Follmann
Frank
F
Andersen
Peter
P
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*
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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