Inactivation of Vacuolating Virus (SV40) by Formaldehyde

Gerber, Paul; Hottle, George A.; Grubbs, R E

doi:10.3181/00379727-108-26892

Cited by 43 publications

(12 citation statements)

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“…As the formalin treatment used to inactivate the poliovirus was only partially effective against SV40 [Gerber et al, 1961], it is estimated that millions of people could have been exposed to live, potentially oncogenic SV40 virus at that time [Shah and Nathanson, 1976]. However, subsequent epidemiological studies failed to find an increased risk of cancer in populations who may have been infected with SV40 by this route [reviewed by Strickler and Goedert, 1998].…”

Section: Introductionmentioning

confidence: 99%

Population‐based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40

Knowles¹,

Pipkin

Andrews³

et al. 2003

Journal of Medical Virology

520

358

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Molecular studies suggest that the simian polyomavirus SV40 is present in the human population, possibly introduced in contaminated polio vaccine. However, no recent seroepidemiological data exist in England on SV40 or on the two human polyomaviruses, BKV and JCV. A comparative age seroprevalence study was undertaken on 2,435 residual sera from 1991 by haemagglutination inhibition (HI) for BKV and JCV, and virus neutralisation for SV40. The overall rates of seropositivity for BKV and JCV were 81% and 35%, respectively, and each was significantly related to age (P < 0.001). BKV seroprevalence reached 91% at 5-9 years of age, but JCV seroprevalence reached only 50% by age 60-69 years. There was a highly significant association between BKV antibody titre and age (P < 0.001), titres decreasing linearly at a rate of 8.7% per 10 years (95% CI = 7.4-10% drop). Significantly more males than females had antibody to JCV (P = 0.013). In individuals under 40 years of age there was a significant negative association between the presence of antibody to BKV and JCV (P < 0.001). By contrast, the antibody prevalence to SV40 remained at 1.3-5% throughout all age groups and titres were low. There was a significant positive association between the presence of antibody to SV40 and antibody to both BKV (P < 0.001) and JCV (P = 0.009), and also to the geometric mean titre (GMT) of BKV antibody (P = 0.011). The results indicate that BKV and JCV are transmitted by different routes. There is no serological evidence that SV40 entered the human population during the past 80 years, and the possibility of cross-reaction with BKV or JCV antibody must be considered.

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Section: Introductionmentioning

confidence: 99%

Population‐based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40

Knowles¹,

Pipkin

Andrews³

et al. 2003

Journal of Medical Virology

520

358

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“…After this initial inactivation the titre of infective virus continued to decrease more slowly over the subsequent test period of 14 days. CELO virus appears to be more efficiently inactivated than another stable potential contaminant of certain vaccines, SV 40 virus; Gerber et al (1961) demonstrated that some SV 40 virus infectivity was retained even after 14 days inactivation at 330 C. with 1/4000 formaldehyde.…”

Section: Discussionmentioning

confidence: 99%

Chick embryo lethal orphan (CELO) virus as a possible contaminant of egg-grown virus vaccines

Oxford

Potter

1969

J. Hyg.

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SUMMARYThe inactivation kinetics of CELO virus were studied in the presence of 1/4000 formaldehyde. Inactivation of the virus by formaldehyde at 4° C. was not complete after 14 days incubation. Formaldehyde inactivation at 36° C., however, was rapid and no virus was detected after 24 hr. incubation.Neutralizing antibody to CELO virus was detected in 20–88% of sera tested from five flocks of hens. This suggested dissemination of the virus in England and Scotland. However, no CELO virus neutralizing antibody at a serum dilution of 1/8 was detected in 142 normal human sera or in 229 sera from persons who had been immunized with egg grown, inactivated influenza virus vaccine.We would like to thank Professor C. H. Stuart-Harris and Drs J. E. Wilson, D. A. Martin and D. Breeze for their help and their criticisms of the manuscript.Dr G. C. Schild kindly supplied a number of the human sera used in the study. The study was financed in part by the National Fund for Research in Poliomyelitis and other Crippling Diseases and by the British Empire Cancer Campaign.

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“…The final step in IPV production involved formalin inactivation of poliovirus. SV40 is relatively resistant to formalin inactivation and thus low levels of live SV40 frequently remained present in lots of IPV [18].…”

Section: Vaccine-related Exposures To Sv40mentioning

confidence: 99%

“…The titer of live SV40 present in IPV varied but was substantially lower than in the cultures from which it was derived. Gerber and colleagues estimated that some IPV doses contained up to 2000 viral particles/ml [18]. The amount of live SV40 that neonates received by injection in a vaccine immunogenicity trial was 10-50 TCID 50 (where TCID 50 is defined as the amount of virus needed to infect 50% of a tissue culture [20]) less than the amount typically required to induce tumors in experimental animals [4].…”

Section: Vaccine-related Exposures To Sv40mentioning

confidence: 99%

“…As for poliovirus vaccines, formalin treatment of the final vaccine product would not have inactivated all of the live SV40 present. In 1961, Gerber and colleagues tested three samples of formalin-inactivated adenovirus vaccine and all contained live SV40 [18]. In addition, 100% of nine evaluated subjects seroconverted to SV40 in one early Army adenovirus vaccine trial [1].…”

Section: Vaccine-related Exposures To Sv40mentioning

confidence: 99%

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Cancer risk associated with receipt of vaccines contaminated with simian virus 40: epidemiologic research

Engels¹

2005

Expert Review of Vaccines

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Simian virus (SV)40 was an accidental contaminant of poliovirus vaccines used widely in the USA and other countries in 1955-1962. Exposure to SV40 via contaminated vaccines has led to concern as SV40 causes cancer in laboratory animals. In addition, some laboratories, although not all, have detected SV40 DNA in human tumors including mesothelioma, certain brain tumors, osteosarcoma and non-Hodgkin's lymphoma. This article reviews the data regarding contamination of poliovirus vaccines with SV40 and summarizes the results from epidemiologic studies of vaccine recipients. Long-term follow-up studies have not revealed recipients of SV40-contaminated poliovirus vaccines to be at an increased risk for cancer. Thus, these studies are somewhat reassuring and indicate that either SV40 does not readily infect humans or, following infection, does not cause cancer. Recognizing that the history of SV40 contamination of vaccines highlights an inherent risk of contamination of vaccines with adventitious agents, the Institute of Medicine recently called for the development of a comprehensive US plan to prevent vaccine contamination and respond to potential contamination events when they arise.

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Inactivation of Vacuolating Virus (SV40) by Formaldehyde

Cited by 43 publications

References 1 publication

Population‐based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40

Population‐based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40

Chick embryo lethal orphan (CELO) virus as a possible contaminant of egg-grown virus vaccines

Cancer risk associated with receipt of vaccines contaminated with simian virus 40: epidemiologic research

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