On January 10, when Chinese researchers published the genome of a mysterious, fast-spreading virus, it confirmed Dan Barouch’s greatest worry. The genome was similar to that of the coronavirus that caused the 2003 SARS outbreak, yet it also had striking differences. “I realized immediately that no one would be immune to it,” says Barouch, director of virology and vaccine research at Beth Israel Deaconess Medical Center in Boston.
Within days, his laboratory and dozens of others around the world started designing vaccines that they hoped could protect billions of people against the SARS-CoV-2 virus, the biggest challenge to global health and prosperity since World War II. By early April, almost 80 companies and institutes in 19 countries were working on vaccines, most gene-based instead of using traditional approaches, such as those that have been employed in influenza vaccines for more than 70 years.
The labs predicted that a commercial vaccine could be available for emergency or compassionate use by early 2021—incredibly fast, given that vaccines to brand-new pathogens have taken a decade to be perfected and deployed. Even the Ebola vaccine, which was fast-tracked, took five years to reach widespread trials. If Barouch and his counterparts can offer a safe, effective concoction in a year, “it will be the fastest vaccine development in history,” he says.
That is a big “if,” however. Although labs have created several gene-based vaccines for other viruses, not one has been commercialized for a human illness.
Alternative Development Methods
The established approach to vaccine development is to grow weakened viruses in chicken eggs—or more recently in mammalian or insect cells—and extract the desired pieces. The process can take four to six months to get the right antigens for familiar viruses that change every year, such as influenza. It can take multiple attempts over years for a new germ. That is far too slow to combat a virus that has already spread to pandemic proportions.
Instead, labs are turning to gene-based vaccines. Scientists use information from the genome of the virus to create a blueprint of select antigens. The blueprint is made of DNA or RNA—molecules that hold genetic instructions. The researchers then inject the DNA or RNA into human cells. The cell’s machinery uses the instructions to make virus antigens that the immune system reacts to. Cells respond to the instructions as a normal part of their daily existence. This is the same trait infectious viruses exploit; they cannot reproduce on their own, so they use a cell’s machinery to make copies of themselves. They burst out of the cell and infect more cells, widening the infection.
In addition to efficacy, the experts are watching the trials for “disease enhancement”—the possibility that a vaccine might inadvertently worsen symptoms of COVID-19, the disease that SARS-CoV-2 causes. Ferrets given an experimental SARS vaccine in 2004 developed damaging inflammation. Kim says humans who were treated with the experimental SARS vaccines did not experience disease enhancement. But those formulations never made it to large-scale human trials because the outbreak—which sickened about 8,000 people in nearly 30 countries—burned out in just over a year.
Companies are accelerating the development time for a SARS-CoV-2 vaccine in part by testing vaccines in multiple animal species at once and in parallel with small numbers of people. Usually the process is one animal at a time, and people later, to make sure that side effects are small, that immune response is large and that disease is actually defeated. Lack of time warrants greater risk.
Global Manufacturing Capacity Like Never Before
Protecting the globe against COVID-19 will require enormous manufacturing capacity. The DNA-plasmid and RNA vaccines have never been scaled up to millions of doses, and small firms such as Inovio and Moderna would not have such capacity in-house. According to Barouch, the adenovirus vaccine is more time-consuming at the outset, but once proved it “can be scaled up quickly.” Johnson & Johnson used an adenovirus approach to generate millions of doses of a vaccine against Ebola, which are now in widespread human trials. A few groups are investigating other DNA techniques that could take longer.
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