Scientists have developed a strain of the
"Our achievement was a combination of synthetic biology and genetic engineering," says co-author Luis Enjuanes of
"The injected vaccine will only replicate in a reduced number of cells and produce enough antigen to immunize the host," he says, and it cannot infect other people, even those in close contact with a vaccinated person.
Enjuanes and his team applied what they had learned from 30 years of research on the molecular biology of coronaviruses to synthesize an infectious cDNA clone of the MERS-CoV genome based on a published sequence. They inserted the viral cDNA chromosome into a bacterial artificial chromosome, and mutated several of its genes, one by one, to study the effects on the virus' ability to infect, replicate, and re-infect cultured human cells.
Mutations that disabled accessory genes 3, 4a, 4b and 5 did not seem to hinder the virus: mutant viruses had similar growth rates as the wild-type virus, indicating that the mutations do not disable the virus enough to deploy the mutants in a vaccine. Mutations in the envelope protein (E protein), on the other hand, enabled the virus to replicate its genetic material, but prevented the virus from propagating, or infecting nearby cells.
A large amount of the rMERS-CoV-I"E virus would be needed for a live attenuated
"To grow the virus, we create what are called 'packaging cells' that express the E protein missing in the virus. The gene to encode this protein is integrated in the cell chromosomes and will not mix with the viral genes. Therefore, in these cells, and only within them, the virus will grow by borrowing the E protein produced by the cell," says Enjuanes. "When the virus in administered to a person for vaccination, this person will not be able to provide the E protein to the defective virus," so the virus will die off after producing antigens to train the human immune system to fight a MERS-CoV infection.
Enjuanes says rMERS-CoV-I"E is a very promising vaccine candidate, but more work remains before they can start clinical trials. He says the mutation in the E protein that prevents the virus from propagating represents one safe guard, but the
The article can be found online at http://bit.ly/mbiotip0913a.
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