Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant
Autor: | Karen Smith Korsholm, Thomas Lindenstrøm, Jonathan Filskov, Kasper Karlsen, Signe Tandrup Schmidt, Marianne Mikkelsen, Peter Andersen, Jon Hansen, Dennis Christensen |
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Rok vydání: | 2014 |
Předmět: |
Skin Neoplasms
Papillomavirus E7 Proteins T cell medicine.medical_treatment CD8-Positive T-Lymphocytes Biology DNA vaccination Viral vector Adjuvants Immunologic Antigen Cations medicine Animals Cytotoxic T cell Cationic liposome Antigens Immunity Cellular Mice Inbred BALB C General Veterinary General Immunology and Microbiology Public Health Environmental and Occupational Health Molecular biology Mice Inbred C57BL Poly I-C Infectious Diseases medicine.anatomical_structure Mice Inbred DBA Liposomes Cancer research Molecular Medicine Female Adjuvant CD8 T-Lymphocytes Cytotoxic |
Zdroj: | Vaccine. 32:3927-3935 |
ISSN: | 0264-410X |
Popis: | Vaccines inducing cytotoxic T-cell responses are required to achieve protection against cancers and intracellular infections such as HIV and Hepatitis C virus. Induction of CD8+ T cell responses in animal models can be achieved by the use of viral vectors or DNA vaccines but so far without much clinical success. Here we describe the novel CD8+ T-cell inducing adjuvant, cationic adjuvant formulation (CAF) 09, consisting of dimethyldioctadecylammonium (DDA)-liposomes stabilized with monomycoloyl glycerol (MMG)-1 and combined with the TLR3 ligand, Poly(I:C). Different antigens from tuberculosis (TB10.3, H56), HIV (Gag p24), HPV (E7) and the model antigen ovalbumin were formulated with CAF09 and administering these vaccines to mice resulted in a high frequency of antigen-specific CD8+ T cells. CAF09 was superior in its ability to induce antigen-specific CD8+ T cells as compared to other previously described CTL-inducing adjuvants, CAF05 (DDA/trehalose dibehenate (TDB)/Poly(I:C)), Aluminium/monophosphoryl lipid-A (MPL) and Montanide/CpG/IL-2. The optimal effect was obtained when the CAF09-adjuvanted vaccine was administered by the i.p. route, whereas s.c. administration primed limited CD8+ T-cell responses. The CD4+ T cells induced by CAF09 were mainly of an effector-memory-like phenotype and the CD8+ T cells were highly cytotoxic. Finally, in a mouse therapeutic skin tumor model, the HPV-16 E7 antigen formulated in CAF09 significantly reduced the growth of already established subcutaneous E7-expressing TC-1 tumors in 38% of the mice and in a corresponding prophylactic model 100% of the mice were protected. Thus, CAF09 is a potent new adjuvant which is able to induce CD8+ T-cell responses against several antigens and to enhance the protective efficacy of an E7 vaccine both in a therapeutic and in a prophylactic tumor model. |
Databáze: | OpenAIRE |
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