Enhancement of immunostimulatory properties of exosomal vaccines by incorporation of fusion-competent G protein of vesicular stomatitis virus.
Exosomes have been proposed as candidates for therapeutic immunization. The present study demonstrates that incorporation of the G protein of vesicular stomatitis virus (VSV-G) into exosome-like vesicles (ELVs) enhances their uptake and induces the maturation of dendritic cells. Targeting of VSV-G and ovalbumin as a model antigen to the same ELVs increased the cross-presentation of ovalbumin via an endosomal acidification mechanism. Immunization of mice with VSV-G and ovalbumin containing ELVs led to an increased IgG2a antibody response, expansion of antigen-specific CD8 T cells, strong in vivo CTL responses, and protection from challenge with ovalbumin expressing tumor cells. Thus, incorporation of VSV-G and targeting of antigens to ELVs are attractive strategies to improve exosomal vaccines.
Temchura
Vladimir V
VV
Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum D-44780, Germany.
Tenbusch
Matthias
M
Nchinda
Godwin
G
Nabi
Ghulam
G
Tippler
Bettina
B
Zelenyuk
Maryna
M
Wildner
Oliver
O
Uberla
Klaus
K
Kuate
Seraphin
S
D000818:Animals; D000906:Antibodies / Q000097:blood; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000517:prevention & control; D010047:Ovalbumin / Q000276:immunology; D021381:Protein Transport; D022142:Secretory Vesicles / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000906:Antibodies; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014612:Vaccines; D014759:Viral Envelope Proteins; D010047:Ovalbumin