Papillomavirus virus-like particles can deliver defined CTL epitopes to the MHC class I pathway.
To evaluate an antigen delivery system in which exogenous antigen can target the major histocompatibility complex (MHC) class I pathway, a single human papillomavirus (HPV) 16 E7 cytotoxic T lymphocyte (CTL) epitope and a single HIV gp160 CTL epitope were separately fused to the C-terminus of bovine papillomavirus 1 (BPV1) L1 sequence to form hybrid BPV1L1 VLPs. Mice immunized with these hybrid VLPs mounted strong CTL responses against the relevant target cells in the absence of any adjuvants. In addition, the CTL responses induced by immunization with BPV1L1/HPV16E7CTL VLPs protected mice against challenge with E7-transformed tumor cells. Furthermore, a high titer-specific antibody response against BPV1L1 VLPs was also induced, and this antiserum could inhibit papillomavirus-induced agglutination of mouse erythrocytes, suggesting that the antibody may recognize conformational determinates relevant to virus neutralization. These data demonstrate that hybrid BPV1L1 VLPs can be used as carriers to target antigenic epitopes to both the MHC class I and class II pathways, providing a promising strategy for the design of vaccines to prevent virus infection, with the potential to elicit therapeutic virus-specific CTL responses.
Peng
S
S
Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Qld., Australia.
Frazer
I H
IH
Fernando
G J
GJ
Zhou
J
J
D000818:Animals; D000917:Antibody Formation; D052688:Bovine papillomavirus 1 / Q000276:immunology*; D002417:Cattle; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D015195:Drug Design; D000939:Epitopes; D005260:Female; D006678:HIV / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology* / Q000517:prevention & control; D014765:Viral Vaccines
D000939:Epitopes; D019302:HIV Envelope Protein gp160; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16