Antibodies to SV40 in Sera from Humans and Macaques

摘要

Poliovaccines manufactured in the 1950s were inadvertently contaminated with the simian polyoma virus SV40, which is a common silent infection of the Rhesus macaque monkeys which supplied the kidneys used to generate the cell cultures used in production. The poliovaccines used were the formalin-killed poliovirus preparations developed by Salk, but SV40 is less sensitive to formalin than poliovirus and it is estimated that 10 to 30 million people were exposed to live SV40 as a result [1]. While othervaccines such as an experimental vaccine against respiratory syncytial virus, and a vaccine used in the military against adenovirus were also contaminated with SV40, the major iatrogenic exposure is from poliovaccines. The virus does not cause a visiblecytopathic effect in Rhesus macaque cell cultures, and was not reported until 1960. By 1962 it is likely that most poliovaccines in use were free of the virus as requirements were introduced to restrict production to animals free of antibodies to SV40, and cultures producing a cytopathic effect after infection were used to screen for it. Subsequent studies using PCR to investigate old retained stocks [2,3] supported the view that poliovaccines used in the U.S.A. and the U.K. were free of SV40 from at least the 1970s. SV40 is known to cause tumours in experimental animals, mainly hamsters [4], and epidemiological studies were undertaken at the time which generally failed to reveal any excess risk of cancer in vaccine recipients [5]. However, the studiestended to be short term. In one a risk to the child was indicated when pregnant women were immunised [5]. In the 1990s, however, SV40 sequences were reported in a number of human tumours, including mesothelioma, osteosarcoma, ependymomas and choroid plexus tumours [6-10]. More recently such sequences have been reported in non-Hodgkin's lymphomas [11,12]. In some cases virus has been isolated [9] suggesting that the patients are indeed infected with SV40. The extent and origin of such infection, if genuine, are matters of great interest. In 1972 Shah reviewed studies on the incidence of antibodies to SV40 in a number of categories of human subjects [13].