Simian Virus 40 (SV40) is a polyomavirus, a family of DNA viruses. Discovered in 1960, its unexpected presence in early vaccine batches was notable. Originally found in rhesus macaques, SV40 has been studied for its potential connections to human health.
Unveiling SV40 and Vaccine Contamination
SV40 was identified in 1960 by Maurice Hilleman and Ben Sweet. The virus was found as a contaminant in polio vaccines. This contamination stemmed from the use of rhesus monkey kidney cells in the production of these early vaccines, as these monkeys can be naturally infected with SV40.
Both the inactivated (Salk) and live attenuated (Sabin) forms of the polio vaccine were affected by SV40 contamination. The methods used to inactivate the polio virus, such as formaldehyde treatment for the Salk vaccine, did not reliably eliminate SV40. This resulted in millions of people being inadvertently exposed to live SV40 through vaccination programs.
In the United States, an estimated 10 million to 30 million individuals received SV40-contaminated polio vaccines between 1955 and early 1963. Beyond polio vaccines, some adenovirus vaccines administered to military personnel from 1961 to 1965 also contained SV40. While the contamination was largely addressed in the U.S. by 1963, some regions, particularly in the former Soviet bloc, may have continued to use contaminated vaccines until the early 1980s, potentially exposing hundreds of millions more globally.
SV40 and Human Health Research
SV40 is classified as a potent DNA tumor virus. In laboratory studies, SV40 has been shown to cause malignancies like sarcomas, ependymomas, leukemias, lymphomas, mesotheliomas, and osteosarcomas in newborn rodents when exposed to high viral levels. The viral replication protein, known as large T antigen (T-ag), is also recognized as a viral oncoprotein.
Research has investigated the presence of SV40 DNA in human tissues and its association with human cancers. Studies have reported detecting SV40 DNA in rare human tumors, including pleural mesothelioma, brain tumors (such as ependymomas and choroid plexus tumors), osteosarcoma, and non-Hodgkin lymphoma. Some research has also indicated that the SV40 T-antigen can bind to human tumor suppressor proteins like p53 and RB, suggesting a possible mechanism for its involvement in cancer development.
Establishing a causal link between SV40 and human diseases remains complex. While numerous reports have identified SV40 DNA in human tumors, not all studies have consistently replicated these findings, with some reporting negative results. The low levels at which SV40 has sometimes been detected in human tissues have also raised questions about its biological role and the possibility of laboratory artifacts. Furthermore, some studies suggest that low-level immunoreactivity to SV40 in human sera might be due to cross-reactivity with antibodies to related human polyomaviruses like BKV and JCV, rather than actual SV40 infection.
Current Understanding and Public Health
Understanding SV40’s prevalence in the human population is still being refined. While some studies suggest that SV40 infections are occurring in both children and adults, including those born after vaccine contamination, prevalence rates vary widely across studies, ranging from 2% to 20% in general populations. Differences in methodology and assay sensitivity contribute to these variations, making exact prevalence difficult to ascertain.
Modern public health practices have evolved to prevent future viral contamination in vaccine production. Since 1963, U.S. polio vaccines have been free of SV40, with strict screening procedures implemented to ensure the virus’s absence in new vaccine lots. Vaccine manufacturing processes are now regulated by agencies like the Food and Drug Administration to ensure viral safety.
The scientific consensus is that while SV40 has properties consistent with a cancer-causing virus in animal models, a definitive causal link to human cancers has not been conclusively established. Epidemiological studies spanning decades, involving millions of people in the U.S. and Europe, have generally not detected an increased cancer risk in those likely to have been exposed to the virus through contaminated vaccines. Some recent reviews indicate that the evidence does not support the notion that SV40 contributed to the development of human cancers.