Scientific Publications by FDA Staff

Cancer Res 2005 Nov 15;65(22):10273-9

Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961.

Cutrone R, Lednicky J, Dunn G, Rizzo P, Bocchetta M, Chumakov K, Minor P, Carbone M

Carbone M, Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Thorac Oncol Program, Room 205,2160 S 1st Ave, Maywood, IL 60153 USA Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Thorac Oncol Program, Maywood, IL 60153 USA Loyola Univ, Cardinal Bernardin Canc Ctr, Breast Canc Program, Maywood, IL 60153 USA Loyola Univ, Virol Lab, Dept Pathol, Maywood, IL 60153 USA US FDA, Rockville, MD 20857 USA

Some polio vaccines prepared from 1954 to 1961 were contaminated with infectious SV40. It has been assumed that all polio vaccines were SV40 free in the United States after 1961 and in other countries after 1962. Following a WHO requirement that was prompted by the detection of SV40 in some human tumors, we conducted a multilaboratory study to test for SV40 polio vaccines prepared after 1961. Vaccine samples from 13 countries and the WHO seed were initially tested by PCR. The possible presence of intact and/or infectious SV40 DNA in PCR-positive samples was tested by transfection and infection of permissive CV-1 cells. All results were verified by immunohistochemistry, cloning, and sequencing. All the vaccines were SV40 free, except for vaccines from a major eastern European manufacturer that contained infectious SV40. We determined that the procedure used by this manufacturer to inactivate SV40 in oral poliovirus vaccine seed stocks based on heat inactivation in the presence of MgCl2 did not completely inactivate SV40. These SV40-contaminated vaccines were produced from early 1960s to about 1978 and were used throughout the world. Our findings underscore the potential risks of using primary monkey cells for preparing poliovirus vaccines, because of the possible contamination with SV40 or other monkey viruses, and emphasize the importance of using well-characterized cell substrates that are free from adventitious agents. Moreover, our results indicate possible geographic differences in SV40 exposure and offer a possible explanation for the different percentage of SV40-positive tumors detected in some laboratories.