Bcr-Abl fusion sequences do not induce immune responses in mice when administered in mouse polyomavirus based virus-like particles.
Mouse polyomavirus-like particles (MPyV-VLPs) carrying inside a fragment of the Bcr-Abl hybrid protein containing the epitope of chronic myeloid leukemia fusion region were prepared. A sequence encoding 171 amino acids covering Bcr-Abl breakpoint was fused to the C-terminal part of VP3 minor protein connecting it to the VP1 capsomeres. Chimeric particles, the Bcr-Abl VLPs, were tested for their ability to induce Bcr-Abl specific immune response in mice after their intranasal (i.n.) or intraperitoneal (i.p.) administration without any other adjuvants. Bcr-Abl VLPs induced strong anti-VP1 immune response in both i.n. and i.p. immunized mice. As expected, neither IgG nor IgM anti-Bcr-Abl specific antibodies were detected in the sera of immunized animals. Surprisingly, no specific CTL (cytotoxic T-lymphocyte) activity was proved using two different methods (in vitro cytotoxicity assay with CFSE-labeled target cells and highly sensitive cytotoxicity assay using MHC class I Bcr-Abl specific pentamers). In addition, no proliferative response of T-cells of i.n. immunized mice after in vitro restimulation with antigen-pulsed bone marrow-derived dendritic cells was observed. Taken together, Bcr-Abl breakpoint epitopes appeared to be weak immunogens and even MPyV-VLPs did not provide sufficient adjuvant ability to support induction of immune responses specific to Bcr-Abl fusion zone epitope.
Hrusková
Veronika
V
Faculty of Science, Charles University in Prague, 128 44 Prague 2, Czech Republic.
Morávková
Alena
A
Babiarová
Katarina
K
Ludvíková
Viera
V
Fric
Jan
J
Vonka
Vladimír
V
Forstová
Jitka
J
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015153:Blotting, Western; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D051379:Mice; D016253:Microscopy, Immunoelectron; D011120:Polyomavirus / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D011994:Recombinant Proteins; D016044:Fusion Proteins, bcr-abl