The translocation motif of hepatitis B virus improves protein vaccination.
Cell-penetrating peptides (CPPs) have been shown to improve antigen loading of dendritic cell vaccines. Here we asked whether fusion of a CPP to a protein improves its immunogenicity when this fusion protein is directly applied as vaccine. We used the cell-penetrating translocation motif (TLM) derived from the hepatitis B virus, because no size limitation of cargos has been observed. Increased immunogenicity was observed when TLM was fused to ovalbumin (TLM-ova). TLM-ova was found to be superior to ova in inducing proliferation and cytotoxicity of ova-specific CD8+ T cells in vitro and in vivo. Using ovalbumin-expressing thymoma cells (EG7-ova), an improved anti-tumor immune response was observed for TLM-ova vaccination versus vaccination with ova. Moreover, TLM-ova vaccination induced a higher titer of anti-ovalbumin IgG2a antibodies compared to ova. These data demonstrate that CPP-protein vaccines can improve cellular as well as humoral immune responses.
Bleifuss
E
E
Robert Koch-Institute, 13353, Berlin, Germany. elke.bleifuss@gsf.de
Kammertoens
T
T
Hutloff
A
A
Quarcoo
D
D
Dorner
M
M
Straub
P
P
Uckert
W
W
Hildt
E
E
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D010047:Ovalbumin