I propose T-cell & antibody based vaccine development against BK virus. It is envisaged that suitably designed active and passive BKV vaccines will also show efficacy against related polyomavirus species JC and SV40. With at least 100,000 transplant procedures performed annually world wide, such a vaccine will result in health care savings of millions of dollars annually.
To highlight the polyomavirus associated disease
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I propose T-cell & antibody based vaccine development against BK virus. It is envisaged that suitably designed active and passive BKV vaccines will also show efficacy against related polyomavirus species JC and SV40. With at least 100,000 transplant procedures performed annually world wide, such a vaccine will result in health care savings of millions of dollars annually.
To highlight the polyomavirus associated disease burden in man, I note that 4.6 to 9.2% of U.S. kidney transplants are complicated by BKV-nephropathy or BK viremia. In addition, BKV causes hemorrhagic cystitis of variable severity in 5-60% of bone marrow transplantation recipients, and 5% of cancer patients treated with chemotherapy. JCV causes progressive multifocal encephalopathy, a functionally devastating and potentially fatal disease, in 0.5 to 5% of acquired immune deficiency syndrome (AIDS) patients. To put this in perspective, the World Health Organization (WHO) estimated 33.2 million HIV infected subjects in the year 2007. JCV has also been associated with human neoplasms, particularly brain tumors and cancer colon. SV40 DNA has been amplified from 40-100% of highly aggressive glial tumors, mesothelioma, and osteogenic sarcomas (estimated incidences of 6.7, 1.1, and 3.0 cases per 100,000 persons respectively, which implies approximately 100,000 affected patients in a world with 7 billion people).
In addition to the aforementioned direct clinical benefits, the proposed vaccine development program will enhance our understanding of interfering T-cells and antibodies that develop during the course of currently evolving gene therapy protocols using polyomavirus protein capsids as a vector.
Development of effective BKV T-cell and antibody based vaccines would eliminate health care costs currently incurred by regular virus screening programs in kidney transplant recipients. Developing a product that also affords protection against JCV and SV40 would be an added bonus. If successful, we have the potential of producing a product that will simultaneously reduce human suffering associated with both infectious disease and malignancy. For cancer patients the vaccine would not be a stand alone intervention, but a potential adjuvant to standard oncology therapies. Indeed, it could be argued that polyomavirus associated tumors are ideal candidates for antigen specific vaccination, since these malignancies express viral encoded tumor specific antigens not expressed by normal tissues.
Conceptually, both prophylactic and therapeutic vaccines can be designed. The best target for a prophylactic vaccine would be a polymer of VP1- protein arranged into 'virus like particles' . These virus-like particles elcit strong neutralizing antibodies, a fact that was exploited in the development of human papillomavirus vaccines. For a therapeutic vaccine we need to induce T-cell mediated immunity against cells already infected by BK virus. A number of viral epitopes on the large T antigen have been recently described and could be used as the starting point for development of a T-cell vaccine.
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