Differences in the effectiveness of delivery of B- and CTL-epitopes incorporated into the hepatitis B core antigen (HBcAg) c/e1-region.
Work from a number of laboratories including our own has shown that foreign B-epitopes inserted into the c/e1-region of Hepatitis B core antigen (HBcAg) elicit powerful antibody responses when mice are immunised with the recombinant core particles. In the present study, we wished to take advantage of the immunodominance of the c/e1-region to deliver cytotoxic T-lymphocyte (CTL) epitopes as a recombinant HBcAg vaccine. Our results indicated that recombinant HBcAg containing CTL epitopes of the E7 protein of human papillomavirus failed to prime E7-directed CTL responses when used to immunise mice for antigen processing through either the endogenous pathway via a Salmonella typhimurium vector, or through the exogenous pathway by parenteral immunisation with recombinant core. Hydropathicity plots predict that the presumed surface location of the hydrophilic c/e1-region within the core particle may alter following insertion of hydrophobic residues constituting the CTL epitopes, thereby compromising their presentation to the afferent immune system. Our data indicate that while the c/e1-region has a powerful adjuvanting effect for inserted B-epitopes, it does not serve this function for inserted CTL epitopes. These findings have generic implications for the development of CTL inducing vaccines using HBcAg as a vaccine vehicle.
Street
M
M
Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston, Queensland, Australia.
Herd
K
K
Londono
P
P
Doan
T
T
Dougan
G
G
Kast
W M
WM
Tindle
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010957:Plasmids; D011994:Recombinant Proteins / Q000276:immunology; D012475:Salmonella / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D015234:HLA-A Antigens; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic