September 10, 2013
Mutant Strain Created From MERS-CoV May Offer Potential Vaccine
Lawrence LeBlond for redOrbit.com - Your Universe Online
Scientists working to find a vaccine and cure for the Middle East Respiratory Syndrome (MERS) coronavirus may have taken a huge step in the right direction.Publishing details in the open-access journal mBio, researchers, led by Luis Enjuanes of the Autonomous University of Madrid, developed a strain of MERS-CoV that may be used as a vaccine against a disease that has so far killed roughly half of all infected patients.
According to the latest data from the World Health Organization (WHO), MERS-CoV has infected at least 114 people worldwide, killing 54 of them. While the total number of cases remains relatively low, the mortality rate is what is most alarming to health experts.
Enjuanes and his colleagues developed the mutant virus, known as rMERS-CoV-ΔE, noting it has a “mutation in its envelope protein that makes it capable of infecting a cell and replicating its genetic material, but deprives it of the ability to spread to other tissues and cause disease.” The authors said once safeguards can be engineered into the virus, it could likely be used as a basis for a safe and effective vaccine against MERS-CoV.
"Our achievement was a combination of synthetic biology and genetic engineering," said Enjuanes in a statement.
"The injected vaccine will only replicate in a reduced number of cells and produce enough antigen to immunize the host," he said, adding that it cannot infect other people, even those in “close contact with a vaccinated person.”
The researchers said that this virus has the potential to evolve the ability to transmit easily between people – it has already shown some unsustainable human-to-human transmission – and could lead to a global pandemic if it does so. While research has, so far, provided a number of antiviral therapies for MERS, a reliable vaccine has yet to be developed.
Through an understanding of 30 years of research on the molecular biology of coronaviruses, Enjuanes and colleagues applied their knowledge to synthesize an infectious cDNA clone of the MERS virus genome based on a published sequence. They then 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.”
While the mutations that disabled accessory genes 3, 4a, 4b and 5 did not seem to hinder the virus, mutations in the envelope protein did enable the virus to replicate its genetic material, yet “prevented the virus from propagating, or infecting nearby cells.”
The researchers noted that a large amount of rMERS-CoV-ΔE virus would be required for a live attenuated MERS vaccine. Basically, a virus that cannot propagate itself could not grow the volume needed without help. The team provided the virus with a supplemental form of an envelope protein.
"To grow the virus, we create what are called 'packaging cells' that express the [envelope 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 [envelope protein] produced by the cell," said Enjuanes. "When the virus in administered [sic] to a person for vaccination, this person will not be able to provide the [envelope protein] to the defective virus." Because of this, the virus will die off after producing antigens to train the human immune system to fight a MERS-CoV infection.
Enjuanes said the mutant virus is a very promising vaccine candidate, but more research is needed before clinical trials can begin. He said the FDA requires that a recombinant live attenuated vaccine strain includes at least three safeguards to ensure the virus cannot revert back to its original virulent form. Currently, Enjuanes’ team can only present one safeguard.
He said his group is working to introduce other disabling mutations in genes that are located in regions of the virus’ genome that are far away from the envelope protein gene to ensure that the virus cannot revert back to the virulent strain.