ANTI-IDIOTYPIC ANTIBODY VACCINES FOR HPV INFECTION

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Human papillomavirus (HPV) gene products are present in most cervical and many anogenital carcinomas. The early lesions caused by these viruses have been shown to progress to carcinomas in some individuals, which demonstrates that certain HPV types play a role in the development of these tumors. A vaccine for protection against HPV infection therefore may decrease the incidence of cervical and anogenital cancers. Such a vaccine is currently unavailable. Our long-term goal is to develop monoclonal anti-idiotypic antibodies (anti-Ids) that antigenically mimic neutralizing epitopes on HPVs and which stimulate a host protective response against HPV infection. The Specific Aims are to use sets of monoclonal antibodies which neutralize HPV type 11 (HPV-11) and cottontail rabbit papillomavirus (CRPV) as antigen to develop a panel of monoclonal anti-Ids. These monoclonal anti-Ids will be tested as (i) immunogens in rabbits and mice for the induction of virus-neutralizing antibodies, and (ii) as probes for the detection of neutralizing antibodies in virus-infected humans and rabbits. We will use two papillomavirus animal model systems for these studies. The athymic mouse xenograft system utilizing HPV-11 infected human foreskin tissue will be used as a model for infection by a human genital papillomavirus type. The CRPV/domestic rabbit system will be used as an animal model which allows for controlled immunizations and deliberate viral challenge; neither of which are possible in the xenograft system. The two papillomavirus models will provide complementary positive and negative control reagents in the form of non-cross-reactive neutralizing and anti-Id monoclonal antibodies for each viral system. This is because these two viruses are host specific in their infectivity, and because the neutralizing epitopes as detected by antibodies are virus-specific.