Cellular and humoral immune responses to chimeric EGFP-pseudocapsids derived from the mouse polyomavirus after their intranasal administration.
Mouse polyomavirus (MPyV) VP1-pseudocapsids carrying enhanced green fluorescent protein (EGFP-VLPs) were used for intranasal immunization of mice. EGFP-VLPs induced strong anti-VP1 but not anti-EGFP antibody production. In vitro restimulation with antigen-pulsed bone marrow-derived dendritic cells (BMDCs) induced remarkable T-cell proliferative response specific for both VP1 and EGFP antigen and IL-2 and IFN-gamma production. Surprisingly, no specific cytotoxic activities against VP1 and EGFP proteins were detected. After intranasal administration of EGFP-VLPs, as well as after polyomavirus infection, a moderate reduction of CD4(+)CD25(+)Foxp3(+) T cells was observed in spleens but not in lymph nodes and peripheral blood, suggesting that both MPyV virions and pseudocapsids are able to induce changes in distribution of regulatory T cells. Treatment of EGFP-VLPs pulsed BMDCs with inhibitors of endosomal acidification proved that presentation of peptides on MHCgp class II is dependent on acidic endosomal environment. Substantial decrease of CD4-specific T-cell proliferation in the presence of proteasome inhibitor suggests that MHCgp class II might load VPL-derived peptides processed by proteasomes. Thus, polyomavirus derived VLPs appear to be promising delivery and adjuvant vehicles for therapeutic proteins.
Fric
Jan
J
Faculty of Science, Charles University in Prague, Prague 2, Czech Republic.
Marek
Martin
M
Hrusková
Veronika
V
Holán
Vladimír
V
Forstová
Jitka
J
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001769:Blood / Q000276:immunology; D036022:Capsid Proteins / Q000008:administration & dosage / Q000276:immunology; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D049452:Green Fluorescent Proteins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D011120:Polyomavirus / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D036022:Capsid Proteins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C062481:VP1 protein, polyomavirus; D022721:Vaccines, Virosome; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma