A live attenuated vaccine contains a mutant strain of a virus that has been derived from a wild-type virulent strain. Vaccines of this type have a number of advantages over most other types of vaccine. One advantage is that there are increasing amounts of virus antigen in the body as the virus replicates. Another is that a wide-ranging immune response is induced that involves B cells, CD4 T cells and CD8 T cells.
There are two properties that the vaccine virus must possess. First, its antigens must be identical, or very similar, to those of the wild-type virus so that an immune response against the vaccine virus provides protection from infection with the wild-type virus. Second, the virulence of the wild-type virus must have been attenuated; in other words the vaccine virus must have little or no virulence.
Most attenuated virus strains have been derived by 'hit and miss' procedures such as repeated passage of wild-type virus in cells unrelated to the normal host. The vaccine strains of the three serotypes of poliovirus (Chapter 14), which are attenuated as a result of their loss of ability to infect neurones, were derived from wild-type strains by passage in monkeys and in monkey kidney cell cultures. Albert Sabin did this pioneering work and the procedure he used to derive one of the attenuated strains is depicted in Figure 24.1. The mutations responsible for attenuation of the three serotypes are now known and some of them are shown in Figure 24.2.
Other attenuated vaccines that have been developed using a similar approach include those for mumps, measles, rubella, yellow fever, canine parvovirus and canine distemper. The attenuated strains of the first three of these, now combined in the MMR vaccine, were all developed by Maurice Hilleman. The mumps virus strain is called Jeryl Lynn after his daughter, from whom the wild-type virus was isolated.
24 passages monkey kidney cells
24 passages attenuated strain
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