Brief Alerts

Contamination of IPV with Oncogenic Simian 40 Virus: We Dodged a Bullet

Source: Strickler HD, et al. Contamination of poliovirus vaccines with simian virus 40 (1955-1963) and subsequent cancer rates. JAMA 1998;279:292-295.

The original inactivated polio vaccine (ipv) was administered to millions of American children between 1955 and l963. IPV was originally produced in cultures of kidney cells of the Asian macaque monkey. It is now known that these vaccines were contaminated with simian virus 40 (SV40). The vaccines were treated with formalin to inactivate live viruses. However, SV40 is relatively resistant to killing by formalin, and IPV contained small, but detectable, amounts of live SV40. SV40 is capable of inducing tumors in experimental animals, and neonatal animals are particularly susceptible. SV40 DNA has recently been detected in several human tumors including ependymomas, osteosarcomas, and mesotheliomas. Strickler and associates from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute performed a retrospective cohort study to examine the incidence of SV40 associated cancers in a large group of American children who had received SV40 contaminated IPV. Birth cohorts that were most likely to have received SV40 contaminated IPV were infants born between 1956 and 1962 and children born between 1947 and 1952. A cohort of children born between 1964 and 1969 were considered non-exposed. Relative risk of developing each of the SV40 associated cancers were determined among exposed and non-exposed cohorts using data from the National Surveillance Epidemiology and End Results program, the Connecticut Tumor Registry, and national mortality statistics. After more than 30 years of follow-up, exposure to SV40 contaminated poliovirus vaccines that were administered by the intramuscular route indicated that there were no increased risks of ependymomas or other brain cancers, osteosarcomas, or mesotheliomas in the United States.

In retrospect, the mass immunization of American children with IPV that was conducted in the mid 1950s is amazing. It is unlikely that a similar program could be carried out today. It was believed that the Salk vaccine was safe. However, we now know that it was contaminated by a potentially oncogenic live virus. The potential for a national catastrophe was real. By 1961, 80-90% of all U.S. children younger than 20 years had received at least one injection of SV40 contaminated IPV.

This reassuring study indicates that we have dodged a bullet. A message for the future is that undiscovered infectious agents are a potential danger in any biologics prepared using human or animal blood or tissues. This danger is well illustrated by the HIV contaminated Factor VIII concentrates that infected three quarters of hemophiliacs receiving them before 1985 and by the contamination of human growth hormone prepared from human pituitary glands with the Creutzfeldt-Jakob virus. More and more, the trend is to develop biologics using recombinant DNA technology, which should go a long way in avoiding these kinds of disasters in the future. -hap