Abstract
Expression of human papillomavirus type 16 (HPV 16) fusion proteins L1ΔCE71–55 and L1ΔCE71–60 (carboxy‐terminal deletion of L1 replaced by 55 or 60 amino‐terminal amino acids of E7) leads to formation of chimeric papillomavirus‐like particles (CVLPs). After “infection” of cells by CVLPs, the chimeric proteins can be detected in the cytosol and the endoplasmic reticulum (ER), suggesting that they are intracellularly processed via the MHC class I pathway and, therefore, able to activate cytotoxic T lymphocytes (CTLs). To investigate the cytotoxic immune response against HPV 16 L1ΔCE71–60 and L1ΔCE71–55 CVLPs, we immunized C57Bl/6 mice with various CVLP doses without adjuvant. Two weeks after immunization, spleen cells were prepared and stimulated in vitro using HPV 16 E7‐expressing transfectants of the tumor cell line RMA. In 51Cr‐release cytotoxicity assays, spleen cells of mice vaccinated with L1ΔCE71–60 CVLPs specifically lysed the RMA‐E7 transfectants as well as RMA cells loaded with the peptide E749–57, which represents an H2‐Db‐restricted CTL epitope. This demonstrates that CVLPs induce an E7‐specific CTL response in mice in the absence of an adjuvant. Furthermore, immunization with CVLPs prevented outgrowth of E7‐expressing tumor cells even if inoculation of cells was performed 2 weeks before vaccination. We conclude from our data that CVLPs show promise for therapy of HPV‐associated lesions. Int. J. Cancer 81:881–888, 1999. © 1999 Wiley‐Liss, Inc.