2004N-0355 - Scientific Considerations Related to Developing Biotechnology Products
FDA Comment Number : EC8
Submitter : Ms. J LeClair Date & Time: 09/23/2004 04:09:13
Organization : Ms. J LeClair
Health Professional
Category :
Issue Areas/Comments
GENERAL
GENERAL
Request to Fast Track with High Priority Cancer Prevention Vaccines
continued from comment 7995).
Cytomegalovirus prevention vaccine (Glioma type primary brain cancer & mental retardation in newborns)
Disease Burden: Cytomegalovirus is the most common vertically transmitted viral infection in the developed world. CMV can be transmitted pre natally (transplacental, in utero acquiring) resulting in congenital CMV infection, natally or in the immediate post natal period. HCMV is the second leading cause of mental retardation in the United States and is a major problem in third world countries. It is also a leading cause of deafness and blindness in children. CMV virus has been recorded by Charles Cobbs recent research in malignant glioma. Malignant gliomas are the most common primary brain tumors in adults, and generally rapidly fatal despite current therapies. Human cytomegalovirus (HCMV) is a B- herpes virus trophic for glial cells that persistently infects 50-90% of the adult human population. HCMV can be reactivated under conditions of inflammation and immunosuppression, and HCMV gene products can dysregulate multiple cellular pathways involved in oncogenesis. Research indicates that a high percentage of malignant gliomas are infected by HCMV and multiple HCMV gene products are expressed in these tumors. Data shows an association between HCMV and malignant gliomas and indicated the HCMV plays an active role in glioma pathogenesis. Mother to child transmission of the virus has been widely reported as well as sexually transmitted transmission. CMV is not very contagious and its horizontal transmission requires close direct contact with infected material, namely secretions that contain the virus.
Vaccines. The current status of CMV vaccines is the subject of several recent reviews. The vaccines tested in clinical trials fall into two categories: subunit vaccines and live attenuated vaccines. The live attenuated vaccines are the Town Vaccine and the Towne-Toledo Chimera vaccines. The subunit vaccines are the glycoprotein B (gB) protein subunit, the canarypox-gB (ALVAC) vaccine, and the canarypox-pp65 (ALVAC) vaccine. Vaccines in both categories have been evaluated for safety and immunogenicity, although to date, none have been evaluated for efficacy against congenital infection and disease. Expert contact on these vaccines and trial information is Dr Mark Schleiss of Cincinnati Children Hospital in Cincinnati, Ohio. (513) 636-8041.