The various attenuated-virus vaccines in current use were developed by rather hit-or-miss methods. However, scientists have been working on a technology — exploiting the phenomenon of codon bias — that may make possible the rational development of safer vaccines.

One group, at Stony Brook University (see J.R. Coleman et al., Science, 27 June 2008), has engineered polio virus with hundreds of mutations in the genes encoding its capsid protein. However, every one of these is a "silent" mutation; that is, it simply changes the codon for the amino acid to a different codon for the same amino acid. When they created polio viruses in which pairs of new codons were ones that the wild polio virus avoids using (because its human host does), they found that the new viruses were far less infectious that the original. But note, that this procedure did not introduce any change in the amino acid sequence of the capsid protein. So one would expect that all the epitopes recognized by the immune system would be unchanged. And, indeed, they went on to show that mice immunized with the synthetic virus were protected from disease caused by the wild virus.

As mentioned above, one of problems associated with the attenuated live virus polio vaccine (Sabin) is the rare back mutation to full virulence. Such back mutation in these engineered viruses would be extremely unlikely considering the hundreds of silent mutations that would have to be reversed.