TY - JOUR
T1 - Papillomavirus virus-like particles can deliver defined CTL epitopes to the MHC class I pathway
AU - Peng, Shiwen
AU - Frazer, Ian H.
AU - Fernando, Germain J.
AU - Zhou, Jian
N1 - Funding Information:
We thank Ms. Trina Stewart for technical assistance in CTL assays, Ms. Kylie Hengst for EM examination, and Mr. Mark Williams for his helpful suggestions and discussion during preparation of this manuscript. This work was funded in part by Grant RO1-CA 57789-01 from NIH, grants from the NHMRC, the Queensland Cancer Foundation, the Maye Bequest, and the Princess Alexandra Hospital Research and Development Foundation.
PY - 1998/1/5
Y1 - 1998/1/5
N2 - 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.
AB - 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.
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U2 - 10.1006/viro.1997.8912
DO - 10.1006/viro.1997.8912
M3 - Article
C2 - 9448699
AN - SCOPUS:0032484471
SN - 0042-6822
VL - 240
SP - 147
EP - 157
JO - Virology
JF - Virology
IS - 1
ER -