E-mail: schillej@dc37a.nci.nih.gov
Dr. Schiller graduated from the University of Wisconsin in Madison with a B.S. in Molecular Biology in 1975. In 1982, he received a Ph.D. from the Department of Microbiology of the University of Washington in Seattle. He joined the Laboratory of Cellular Oncology as a National Research Service Award Postdoctoral Fellow in 1983. Dr. Schiller became a Senior Staff Fellow in the LCO in 1986 and assumed his current position of Senior Investigator in 1992.
Papillomaviruses (PVs) infect the squamous epithelia of a wide variety of animals and man. Infections are species specific and generally induce localized benign proliferation. However, the lesions induced by certain PVs can undergo malignant progression. There is a strong association between malignant progression of human genital lesions and certain human (H) PV types, most frequently HPV16. The major goals of the laboratory have been to elucidate the role of HPVs in the genesis of human cancers and to develop safe and effective vaccines to prevent genital HPV induced disease.
Difficulties in studying PV virions, due to the lack of efficient in vitro propagation methods, were partially overcome by our recent demonstration that the virion proteins can self-assemble into virus-like particles (VLPs) when over-expressed in eukaryotic cells. Three types of studies based upon the VLP technology are being conducted. First, questions into the basic biology and biochemistry of virion assembly and infection are being examined. We have determined that the L1 major capsid protein alone has the capacity to self- assemble into structures that closely resemble authentic virions. The L2 minor capsid protein is required for infection and genome packaging, but is not required for interaction with the virus cell surface receptor.
Second, studies of genital HPV natural history and disease association are being conducted using a VLP-based ELISA that we recently developed. This is the first HPV serologic assay to be specifically associated with detection of genital tract HPV DNA, lifetime number of sex partners and cervical neoplasia in women, and with relative risk of cervical cancer in populations. In cross-sectional case-control studies, HPV16 virion antibodies were found to be strongly associated with cervical, vulvar, and anal, and (unexpectedly) with esophageal cancers but not penile cancer. In prospective studies, seropositivity was strongly associated with the subsequent development of cervical and again esophageal cancer, but not laryngeal or oral cancers.
Third, an HPV VLP-based prophylactic vaccine is being developed to prevent cervical and other genital HPV-associated cancers. We and our colleagues have demonstrated type-specific protection from high dose experimental infection after VLP vaccination in rabbit and cattle models. To facilitate the evaluation of immune responses in human vaccine trials, we have developed an in vitro infectivity and neutralization assay for HPV16, as well as rapid VLP-based hemagglutination inhibition assays, which in the animal models correlate well with protection. The possibility that VLPs of one type could cross- protect against infection by other types has been evaluated using these assays. The results strongly suggest that protection in VLP-based vaccines in humans will primarily be type specific.
Representative Publications
Last revised on April 14, 1997.
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