Epitope-specific antibody response to Mel-CAM induced by mimotope immunization.
Peptide mimotopes of tumor antigen epitopes have been proposed as components of tumor vaccines. In this study, we determined the immunogenicity of melcam mim1 and melcam mim2, peptide mimics of an epitope of the melanoma cell-adhesion molecule (Mel-CAM). BALB/c mice were vaccinated either with mimotopes or mimotopes coupled to tetanus toxoid (TT). The antibody responses of mice to melcam mim1, melcam mim2, and recombinant Mel-CAM were analyzed by an ELISA and immunoblot analyses. TT-coupled mimotopes led to high titers of IgG mainly of the IgG2a subclass to melcam mim1 and melcam mim2. Immunization with each of the mimotope formulations induced antibodies that cross-reacted with recombinant Mel-CAM. Uncoupled mimotopes induced lymphocyte proliferation and cytokine production in spleen cell cultures indicating that both peptide mimotopes also contained T cell epitopes. TT-coupled mimotopes induced T helper (Th)1 (interleukin (IL)-2, interferon-gamma) and Th2 (IL-4, IL-5) cytokines, whereas uncoupled mimotopes induced a Th1-biased T cell response. Our results suggest that mimotopes potentially represent a novel vaccine approach to induce a tumor antigen-specific humoral and cellular response.
Hafner
Christine
C
Department of Dermatology, Division of General Dermatology, Medical University of Vienna, Austria.
Wagner
Stefan
S
Jasinska
Joanna
J
Allwardt
Dorothee
D
Scheiner
Otto
O
Wolff
Klaus
K
Pehamberger
Hubert
H
Wiedermann
Ursula
U
Breiteneder
Heimo
H
D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012878:Skin Neoplasms / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000939:Epitopes; D013745:Tetanus Toxoid; D003165:Complement System Proteins