HBsAg-vectored vaccines simultaneously deliver CTL responses to protective epitopes from multiple viral pathogens.
We have previously demonstrated that the potent immunogenicity of hepatitis B surface antigen (HBsAg) may be exploited to deliver foreign antigens for cytotoxic T-lymphocyte (CTL) induction. Here we demonstrate that a single low-dose immunization with rHBsAg DNA is sufficient to prime for CTL responses against encoded foreign epitope and that the responses may be recalled many months after immunization. We show that simultaneous disease-protective CTL responses restricted through a diversity of MHC class I haplotypes are elicited by recombinant (r) HBsAg DNA containing multiple viral epitopes appended as a C'-terminal polyepitope or encoded individually within the HBsAg polypeptide. CTL responses delivered by rHBsAg DNA were elicited in the presence of HBsAg-directed antibody. These studies vindicate the use of HBsAg as a powerful vector to deliver CTL responses to foreign antigen and have implications for a multidisease vaccine applicable to an MHC-polymorphic population.
Chen
Dekun
D
Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital and Clinical Medical Virology Centre, University of Queensland, Brisbane, Australia.Shaanxi, Yangling, China. Chendekun163@163.com
Edgtton
Kristy
K
Gould
Allan
A
Guo
Huayang
H
Mather
Michael
M
Haigh
Oscar
O
Cochrane
Melanie
M
Kattenbelt
Jacqueline
J
Thomson
Scott
S
Tindle
Robert
R
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000276:immunology; D004274:DNA, Recombinant; D004279:DNA, Viral; D015828:Eye Infections, Viral; D005260:Female; D006514:Hepatitis B Surface Antigens; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000957:Antigens, Viral, Tumor; D004274:DNA, Recombinant; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D014614:Vaccines, Synthetic; D014765:Viral Vaccines