# 7747
Later today, the online open-access journal mBio will publish a report on the development of a genetically engineered MERS-CoV strain that could be used in vaccine research. While a substantial technological achievement, and a welcome sign of progress, this is but an early step in the development of a MERS vaccine.
A process that is more likely to be measured in years, than in months.
While the creation of a vaccine candidate MERS strain is an important first step, as we’ve seen previously (see Challenges To Developing A Coronavirus Vaccine), after 10 years of trying, no safe and effective vaccine against the SARS virus (another coronavirus) has yet been produced.
In 2012, a PLoS One research article (cite Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus) found that mice vaccinated with four different experimental SARS candidate vaccines developed the expected antibodies, but experienced lung damage when challenged with the virus.
Unlike an influenza vaccine, with which we have more than 6 decades of experience, there is much we don’t know about the safety, effectiveness, and creation of a coronavirus vaccine.
The mBio article has not yet been published,so I’ll update this post with a direct link to the article when it goes live (UPDATED).
Fernando Almaz�n, Marta L. DeDiego, Isabel Sola, Sonia Zu�iga, Jose L. Nieto-Torres, Silvia Marquez-Jurado, German Andr�s and Luis Enjuanes
doi:10.1128/mBio.00650-13
Below, we have a press release from the American Society for Microbiology, after which I’ll return with a few additional comments.
Scientists engineer strain of MERS coronavirus for use in a vaccine
Scientists have developed a strain of the Middle East respiratory syndrome coronavirus (MERS-CoV) that could be used as a vaccine against the disease, according to a study to be published in mBio®, the online open-access journal of the American Society for Microbiology. The mutant MERS virus, rMERS-CoV-ΔE, 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 say once additional safe guards are engineered into the virus, it could be used as the basis of a safe and effective live-attenuated vaccine against MERS.
"Our achievement was a combination of synthetic biology and genetic engineering," says co-author Luis Enjuanes of The Autonomous University of Madrid (Universidad Autónoma de Madrid).
"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.
Since MERS was first identified in June 2012, the World Health Organization has been notified of 108 cases of infection, including 50 deaths. Although the total number of cases is still relatively small, the case fatality rate and the spread of the virus to countries beyond the Middle East is alarming to public health officials. If the virus evolves the ability to transmit easily from person to person, a much more widespread epidemic is possible. Diagnostic assays and antiviral therapies for MERS have been described, but reliable vaccines have not yet been developed.
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-ΔE virus would be needed for a live attenuated MERS vaccine. A virus that can't propagate itself would be unable to grow the volume needed without help. Enjuanes says they provided the virus with a supplemental form E protein.
"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-ΔE 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 US Food and Drug Administration requires that a recombinant live attenuated vaccine strains include at least three safe guards to ensure the virus doesn't revert easily back to its virulent form. His group is currently working on introducing other disabling mutations in genes that are located in regions of the virus' genome that are far away from the E protein gene to ensure the virus cannot revert back to virulence in a single recombination event.
In just about every book, movie, or TV show about a deadly virus, scientists cobble together some last-minute vaccine, produce it in quantity, and distribute it in the nick of time to save the world. In my review of the movie Contagion (see Why You Should Catch `Contagion’) I praised it for a realistic portrayal (with some dramatic license) of how the CDC would tackle an outbreak of a novel zoonotic virus.
My biggest quibble with the film was the speed with which an experimental vaccine is developed, manufactured, and begins to be delivered.
It is a lovely idea, and a handy resolution for any disaster movie, but it suffers from one fatal flaw: We’ve neither the manufacturing technology, capacity, or the vaccine dispensing infrastructure - to pull off such a feat.
Technology is advancing, and so what is not feasible today may become possible tomorrow. But for now, the odds of seeing large quantities of a MERS-CoV vaccine available for the public anytime soon seems pretty remote. None of which is to suggest that the development of a MERS vaccine is a waste of time.
Should MERS become a humanized pathogen, then a vaccine could be a genuine lifesaver, even if not available for some time. And what we learn about a MERS vaccine today could help us develop vaccines for other emerging diseases in the future.
But for now, our first line of defense in any pandemic is not going to be a shot or a pill, it is a range of steps collectively called NPIs, or Non Pharmaceutical Interventions.
The CDC’s Nonpharmaceutical Interventions (NPIs) webpage defines NPIs as:
Nonpharmaceutical interventions (NPIs) are actions, apart from getting vaccinated and taking medicine, that people and communities can take to help slow the spread of illnesses like influenza (flu). NPIs are also known as community mitigation strategies.
NPIs are geared to the virulence and spread of the virus, and may range from simple advice to `wash your hands and cover your coughs’ to mandatory school and business closings.
Should the novel coronavirus, H7N9, or any other novel virus threaten, we’ll be talking a lot about NPIs, and their efficacy, impact, and practicality in the blog.
