Live Attenuated vaccines

It is generally accepted that live vaccines are the preferred vaccines and examples are shown in Table 1. Initially these vaccines were derived by the continued passage of the virulent wild-type (natural) virus in cultured cells and selecting for avirulent viruses that would replicate in vivo but not cause disease. The replication of avirulent virus triggers the immune system, which not only eliminates this virus from the host but also establishes immune memory that serves to resist the virulent wild-type virus. A vac- cine created in this way during the 1950s, the Sabin poliovirus vaccine, is still in use today. Attenuation is the result of genetic mutation and of course viruses can therefore mutate again in such a way that they revert back to the wild-type genotype and phenotype (i.e. revert back to full virulence). Recent experiments have shown that, for poliovirus type 3, reversion to a virulent form involves only two amino acid changes. The problem of reversion has meant that this rather empirical approach of virus attenuation has now been replaced by defined genetic manipulation of viruses either deleting or mutating individual genes. The risk of reversion with these vaccines is minimal.

Live vaccines have distinct advantages over killed. They require only  small  amounts of input virus (which must replicate), they  can  induce local  immunity (i.e. mucosal antibody), they  may  be given  by the  natural route of infection (for example, the  Sabin  vaccine  is given orally), and  they  are usually less expensive. Drawbacks to their use include the  problem of reversion to virulence as described above, a loss  of effectiveness if not kept live (usually requiring refrigeration or freeze-drying), and poor effectiveness in individuals with  other infections – for example, infections of the  gut  inhibit replication of the poliovirus vaccine.

             Additionally, contamination with other adventitious agents can cause serious problems and live vaccines are of course limited to use in only immunocompetent individuals.