Live Attenuated Vaccines
Before the introduction of recombinant-DNA (rDNA) technology, a first step to improved live vaccines was the attenuation of virulent microorganisms by serial passage and selection of mutant strains with reduced virulence or toxicity. Examples are vaccine strains for oral polio vaccine, measles-rubella-mumps (MMR) combination vaccine, and tuberculosis vaccine con-sisting of bacille Calmette-Gue´rin (BCG). An alter-native approach is chemical mutagenesis. For instance, by treating Salmonella typhi with nitrosogua-nidine, a mutant strain lacking some enzymes that are responsible for the virulence was isolated (Germanier and Fuer, 1975).
Live attenuated organisms have a number of advantages as vaccines over non-living vaccines. After administration, live vaccines may replicate in the host similar to their pathogenic counterparts. This confronts the host with a larger and more sustained dose of antigen, which means that few and low doses are required. In general, the vaccines give long-lasting humoral and cell-mediated immunity.
Live vaccines also have drawbacks. Live viral vaccines bear the risk that the nucleic acid is incorporated into the host’s genome. Moreover, reversion to a virulent form may occur, although this is unlikely when the attenuated seed strain contains several mutations. Nevertheless, for diseases such as viral hepatitis, AIDS and cancer, this drawback makes the use of conventional live vaccines virtually unthinkable. Furthermore, it is important to recognize that immunization of immunodeficient children with live organisms can lead to serious complications. For instance, a child with T-cell deficiency may become overwhelmed with BCG and die.
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