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Progress in vaccination
During the lifetime of the author, vaccination has evolved in the complexity of its targets and the technologies used to overcome that complexity. This point is illustrated using the development of several vaccines. Rubella was, and in some countries still is, a major cause of birth defects when infection occurs during pregnancy. In order to prevent infection by a wild virus, a strain was isolated from a congenital infection and attenuated by passage in human fibroblasts at low temperature. The resultant virus was attenuated and could immunize mothers and thus prevent congenital infection and abnormalities. Although rabies vaccines had been developed in the nineteenth century, the available vaccines were poorly immunogenic and sometimes failed to protect. The virus was adapted to cell culture and inactivated with beta-propiolactone. This resulted in highly immunogenic vaccines that can protect after three or four doses only. Infantile gastroenteritis is a problem throughout the world and its major cause is the rotaviruses. In order to prevent infection, a bovine rotavirus was combined with antigens from human strains by the technique of reassortment of segmented RNA. The resulting vaccine was attenuated but could infect infants and generate protective responses at the intestinal level. Finally, cytomegalovirus is now the number one infectious cause of congenital abnormalities. To prevent this virus from infecting pregnant women, a variety of approaches are being taken to develop a vaccine, including using glycoproteins from the virus, developing vaccine replication-defective strains and DNA plasmids.