Cellular and humoral immune responses to chimeric EGFP-pseudocapsids derived from the mouse polyomavirus after their intranasal administration

• DOI: 10.1016/j.vaccine.2008.04.006
• Publication Date: 2008-04-24T14:39:55Z
• Authors: Jan Frič; Martin Marek; Veronika Hrušková; Vladimír Holáň; Jitka Forstová
• Keywords: 0303 health sciences; Recombinant Fusion Proteins; T-Lymphocytes; Green Fluorescent Proteins; Antibodies, Viral; Cytotoxicity Tests, Immunologic; 3. Good health; Vaccines, Virosome; Interferon-gamma; Mice; 03 medical and health sciences; Blood; T-Lymphocyte Subsets; Animals; Interleukin-2; Capsid Proteins; Female; Lymph Nodes; Polyomavirus; Administration, Intranasal; Spleen; Cell Proliferation; T-Lymphocytes, Cytotoxic

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.