Multiple copies of a tumor epitope in a recombinant hepatitis B surface antigen (HBsAg) vaccine enhance CTL responses, but not tumor protection.
We propose the replacement of endogenous epitopes with foreign epitopes to exploit the highly immunogenic hepatitis B surface antigen (HBsAg) as a vaccine vector to elicit disease-protective cytotoxic T-lymphocyte (CTL) responses. Locations were defined within the HBsAg gene where replacements of DNA encoding HBsAg epitopes may be made to generate functional recombinant (r) HBsAg DNA vaccines. We demonstrate that rHBsAg DNA vaccines encoding multiple copies of a model tumor epitope from human papillomavirus (HPV) elicit enhanced CTL responses compared to rHBsAg DNA vaccines encoding a single copy. We show that rHBsAg DNA vaccines elicit a marked prophylactic and long-lived therapeutic protection against epitope expressing tumor, although protective efficacy was not improved by increasing the number of copies of the tumor epitope DNA. These results demonstrate the efficacy of HBsAg as a vector for the delivery of foreign CTL epitopes using the epitope replacement strategy, and have implications for rHBsAg vaccine design. The results also have implications for the derivation of a therapeutic vaccine for HPV-associated squamous carcinoma.
Haigh
Oscar
O
Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital Herston Road, Herston, QLD 4029, Australia.
Guo
Huayang
H
Edgtton
Kristy
K
Mather
Michael
M
Herd
Karen A
KA
Tindle
Robert W
RW
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000517:prevention & control; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D018628:Gene Dosage; D005822:Genetic Vectors; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16