Review of accidents caused by incomplete inactivation of viruses

Inactivation of viruses and bacterial toxins with formaldehyde for the preparation of vaccines has been a favourite method for most of this century. The Cutter incident in 1955 with poliovaccine focussed attention on the problems accompanying the procedure for inactivating viruses although it had been known since the 1930s that the method was not without its dangers. It had also been known since about the same time that foot-and-mouth disease vaccines prepared in this way could carry residual infectivity. The molecular methods of analysis introduced in the 1970s proved without any doubt that the outbreaks in France in 1981 and in other countries of Western Europe in the 1980s were caused by improperly inactivated vaccines. Recent molecular evidence has now shown that formaldehyde-inactivated Venezuelan equine encephalitis vaccines were the probable cause of the outbreaks of the disease during the 1969-1972 pandemic in Central America. In the author's opinion it is remarkable that formaldehyde is still used for the preparation of inactivated vaccines, particularly since it is known that the procedure also affects the immunogenic epitopes of the viruses.