Creating Live Attenuated Vaccine by modifying viral genomic sequence

Attenuated vaccine is created by mechanism in which the virus is weakened so they do not ellicit pathogenicity but strong enough to induce the immune response for attacking the virus. The vaccine could be created by several ways, like by exposing the virus through series of chemical or physical treatments, so that the virus lose its capability to infect. A new promosing method for making the live attenuated vaccine is being offered by altering the genetic code of virus yet the virus is still have similar protein profile. I will try to elucidate the underlying reasoning in this essay.

For those who do not know, the genetic is read by three letters basis, so called as codon. One codon consists of three nucleotides translates into one amino acid and attached together to produce protein. However, the codon is redundant or one amino acid could be originated from different codon. This is stemmed from the fact that there are 64 possible combinations of four DNA letters (A,T,G and C) in three codon position yet the type of natural amino acid in protein is only about 20.

Interesting feature is found from this fact, it is turned out that different organisms prefer to use particular codon in their genome to produce the protein ( it means that the availibility of tRNA specific for the codon is not equal for all combinations of codon). The DNA sequences are different in plants, animals and bacteria, even though they code for the same protein. This phenomenon so called as codon bias, has been proposed to be harnessed as cell mechanism to inhibit the replication of pathogen in the infected host.

As a rule of thumb, pathogens keep evolving so that the mechanism then followed by adaptation of the virus to minimize the inhibition. Research result indicates that the human infected virus has the codon usage match with the host they infected. This exemplify the evolutionary arms race at the work.

By examining this phenomenon, it has been proposed a novel vaccine design strategy by creating artificial virus which has codon usage far different from the host, so that the virus will not replicate efficiently and as a result will lost its virulence. The vaccine is expected to provide immunity to the whole epitope found in this virus, so it provides a strong immune protection.

This article is based on this PNAS article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403163/

 

 

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