Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes.
Although hepatitis B surface antigen (HBsAg) per se is highly immunogenic, its use as a vector for the delivery of foreign cytotoxic T-lymphocyte (CTL) epitopes has met with little success because of constraints on HBsAg stability and secretion imposed by the insertion of foreign sequence into critical hydrophobic/amphipathic regions. Using a strategy entailing deletion of DNA encoding HBsAg-specific CTL epitopes and replacement with DNA encoding foreign CTL epitopes, we have derived chimeric HBsAg DNA immunogens which elicited effector and memory CTL responses in vitro, and pathogen- and tumor-protective responses in vivo, when the chimeric HBsAg DNAs were used to immunize mice. We further show that HBsAg DNA recombinant for both respiratory syncytial virus and human papillomavirus CTL epitopes elicited simultaneous responses to both pathogens. These data demonstrate the efficacy of HBsAg DNA as a vector for the delivery of disease-relevant protective CTL responses. They also suggest the applicability of the approach of deriving chimeric HBsAg DNA immunogens simultaneously encoding protective CTL epitopes for multiple diseases. The DNAs we tested formed chimeric HBsAg virus-like particles (VLPs). Thus, our results have implications for the development of vaccination strategies using either chimeric HBsAg DNA or VLP vaccines. HBsAg is the globally administered vaccine for hepatitis B virus infection, inviting its usage as a vector for the delivery of immunogens from other diseases.
Woo
Wai-Ping
WP
Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston Road, Herston, QLD 4029, Australia.
Doan
Tracy
T
Herd
Karen A
KA
Netter
Hans-Jürgen
HJ
Tindle
Robert W
RW
D000595:Amino Acid Sequence; D000818:Animals; D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000502:physiology
D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D022261:Respiratory Syncytial Virus Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma