This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cutrone, R. Articles by Carbone, M. Search for Related Content PubMed PubMed Citation Articles by Cutrone, R. Articles by Carbone, M.

Some Oral Poliovirus Vaccines Were Contaminated with Infectious SV40 after 1961

¹ Thoracic Oncology Program and ² Breast Cancer Program, Cardinal Bernardin Cancer Center, and ³ Laboratory of Virology, Department of Pathology, Loyola University, Chicago, Illinois; ⁴ National Institute for Biological Standards and Control, Herts, United Kingdom; and ⁵ Food and Drug Administration, Rockville, Maryland

Requests for reprints: Michele Carbone, Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago Medical Center, Room 205, 2160 South First Avenue, Maywood, IL 60153. Phone: 708-327-3250; Fax: 708-327-3238; E-mail: mcarbon{at}lumc.edu.

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.

This article has been cited by other articles:

				V. Sroller, R. A. Vilchez, A. R. Stewart, C. Wong, and J. S. Butel Influence of the Viral Regulatory Region on Tumor Induction by Simian Virus 40 in Hamsters J. Virol., January 15, 2008; 82(2): 871 - 879. [Abstract] [Full Text] [PDF]

				P. Bertino, F. Piccardi, C. Porta, R. Favoni, M. Cilli, L. Mutti, and G. Gaudino Imatinib Mesylate Enhances Therapeutic Effects of Gemcitabine in Human Malignant Mesothelioma Xenografts Clin. Cancer Res., January 15, 2008; 14(2): 541 - 548. [Abstract] [Full Text] [PDF]

				M. Comar, C. Rizzardi, R. de Zotti, M. Melato, M. Bovenzi, J. S. Butel, and C. Campello SV40 Multiple Tissue Infection and Asbestos Exposure in a Hyperendemic Area for Malignant Mesothelioma Cancer Res., September 15, 2007; 67(18): 8456 - 8459. [Abstract] [Full Text] [PDF]

				A. Cristaudo, R. Foddis, A. Vivaldi, G. Guglielmi, N. Dipalma, R. Filiberti, M. Neri, M. Ceppi, M. Paganuzzi, G. P. Ivaldi, et al. Clinical Significance of Serum Mesothelin in Patients with Mesothelioma and Lung Cancer Clin. Cancer Res., September 1, 2007; 13(17): 5076 - 5081. [Abstract] [Full Text] [PDF]

				C. Robinson, I. van Bruggen, A. Segal, M. Dunham, A. Sherwood, F. Koentgen, B. W.S. Robinson, and R. A. Lake A Novel SV40 TAg Transgenic Model of Asbestos-Induced Mesothelioma: Malignant Transformation Is Dose Dependent. Cancer Res., November 15, 2006; 66(22): 10786 - 10794. [Abstract] [Full Text] [PDF]

				B. Kroczynska, R. Cutrone, M. Bocchetta, H. Yang, A. G. Elmishad, P. Vacek, M. Ramos-Nino, B. T. Mossman, H. I. Pass, and M. Carbone Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters PNAS, September 19, 2006; 103(38): 14128 - 14133. [Abstract] [Full Text] [PDF]

				D. L. Poulin and J. A. DeCaprio Is There a Role for SV40 in Human Cancer? J. Clin. Oncol., September 10, 2006; 24(26): 4356 - 4365. [Abstract] [Full Text] [PDF]

				K. S. Rosenthal and D. H. Zimmerman Vaccines: all things considered. Clin. Vaccine Immunol., August 1, 2006; 13(8): 821 - 829. [Full Text] [PDF]