A novel liposome-based adjuvant CAF01 for induction of CD8(+) cytotoxic T-lymphocytes (CTL) to HIV-1 minimal CTL peptides in HLA-A*0201 transgenic mice.
BACKGROUND
Specific cellular cytotoxic immune responses (CTL) are important in combating viral diseases and a highly desirable feature in the development of targeted HIV vaccines. Adjuvants are key components in vaccines and may assist the HIV immunogens in inducing the desired CTL responses. In search for appropriate adjuvants for CD8(+) T cells it is important to measure the necessary immunological features e.g. functional cell killing/lysis in addition to immunological markers that can be monitored by simple immunological laboratory methods.


RESULTS
We tested the ability of a novel two component adjuvant, CAF01, consisting of the immune stimulating synthetic glycolipid TDB (Trehalose-Dibehenate) incorporated into cationic DDA (Dimethyldioctadecylammonium bromide) liposomes to induce CD8(+) T-cell restricted cellular immune responses towards subdominant minimal HLA-A0201-restricted CTL epitopes from HIV-1 proteins in HLA-A*0201 transgenic HHD mice. CAF01 has an acceptable safety profile and is used in preclinical development of vaccines against HIV-1, malaria and tuberculosis.


CONCLUSIONS
We found that CAF01 induced cellular immune responses against HIV-1 minimal CTL epitopes in HLA-A*0201 transgenic mice to levels comparable with that of incomplete Freund's adjuvant.
Gram
Gregers Jacob
GJ
Department of Virology, Statens Serum Institut, Copenhagen, Denmark.
Karlsson
Ingrid
I
Agger
Else Marie
EM
Andersen
Peter
P
Fomsgaard
Anders
A
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D005620:Freund's Adjuvant / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry*; D015497:HIV-1 / Q000378:metabolism*; D015234:HLA-A Antigens / Q000096:biosynthesis*; D015789:HLA-A2 Antigen; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013601:T-Lymphocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000276:Adjuvants, Immunologic; D000939:Epitopes; D006017:Glycolipids; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; C507803:trehalose 6,6'-dibehenate; C015831:dimethyldioctadecylammonium; D005620:Freund's Adjuvant