Papillomavirus-like particles (VLPs) are a promising prophylactic
vaccine candidate to prevent human papillomavirus (HPV)
infections and associated epithelial
neoplasia. However, they are unlikely to have
therapeutic effects because the virion
capsid proteins are not detected in the proliferating cells of the infected epithelia or in cervical
carcinomas. To increase the number of
viral antigen targets for cell-mediated immune responses in a VLP-based
vaccine, we have generated stable chimeric VLPs consisting of the L1 major
capsid protein plus the entire E7 (11 kDa) or E2 (43 kDa) nonstructural papillomavirus
protein fused to the L2 minor
capsid protein. The chimeric VLPs are indistinguishable from the parental VLPs in their morphology and in their ability to agglutinate erythrocytes and elicit high titers of
neutralizing antibodies. Protection from
tumor challenge was tested in C57BL/6 mice by using the tumor cell line TC-1, which expresses HPV16 E7, but not the virion structural
proteins. Injection of HPV16 L1/L2-HPV16 E7 chimeric VLPs, but not HPV16 L1/L2 VLPs, protected the mice from
tumor challenge, even in the absence of adjuvant. The chimeric VLPs also induced protection against
tumor challenge in major histocompatibility class II-deficient mice, but not in beta2-microglobulin or
perforin knockout mice implying that protection was mediated by class I-restricted cytotoxic lymphocytes. These findings raise the possibility that VLPs may generally be efficient vehicles for generating cell-mediated immune responses and that, specifically, chimeric VLPs containing papillomavirus nonstructural
proteins may increase the therapeutic potential of VLP-based prophylactic
vaccines in humans.