Faraz Zaidi and Daniel Park peered at a series of small, black blots that appeared on a clear sheet of plastic — confirming they had created a type of protein that, until January, was unknown to science.
It was alerting them to the presence of the microscopic "spikes" on a coronavirus.
From the moment the Chinese government published the microbe's genetic code in January, scientists such as Zaidi and Park have been racing to develop a vaccine. The pair work in the lab of David B. Weiner at Philadelphia's Wistar Institute, which is collaborating with Inovio Pharmaceuticals and others to deliver a vaccine within months. That's a fast timetable, made possible by an approach Weiner helped pioneer.
Unlike traditional vaccines, which contain killed or weakened forms of the virus in question, Inovio's product contains genetic instructions to make just a fragment of a virus: a single type of protein.
The old method requires extensive testing to ensure the weakened viruses will not make anyone sick. The newer DNA vaccines can be proven safe much more quickly, said Weiner, who serves on Inovio's board. "If you wanted to do this the old-fashioned way, we'd be talking about a many year project," he said.
Whether the immune system is being exposed to a weakened or killed virus, or just a fragment, the goal is the same: teaching the body to defend itself should it ever encounter a real infection.
Several other teams around the world also are working on a vaccine. People who become infected with coronavirus tend to develop mild symptoms such as a cough, and recover on their own. But a minority of patients have come down with severe, pneumonia-like symptoms.
Inovio scientists "printed" their vaccine in hours with a DNA synthesizer: a computerized system that fuses chemical base pairs in the correct order. However, testing its safety and effectiveness in humans will take months.
In the lab, Zaidi and Park were testing one of several versions of the vaccine — verifying that the instructions would cause the correct proteins to be made. Other tests were underway to ensure that the proteins were triggering an immune response, in the form of white blood cells called T-cells.
The proteins are the ones that give the coronavirus family its name: the spikes on the outer edge of each virus particle, giving the appearance of a corona, or crown, like the fringe surrounding a solar eclipse.
Other viruses for which vaccines have been made with this approach include Ebola, HIV and MERS, a different type of coronavirus.
These DNA vaccines are not administered in the usual way, because if you simply injected DNA into a person's bloodstream, enzymes would degrade it before it had a chance to penetrate cells.
Instead, DNA vaccines are administered with a device that has several metal probes on the end. The probes are placed against the skin, delivering a small electric current that opens tiny pores in skin cells, Weiner said.
These cellular "micropores" remain open for just a split second, long enough to take in about 1,000 copies of the necessary DNA instructions in each cell. The vaccine remains confined to cells in that immediate patch of skin. "It's all just local," Weiner said.
The cells then make the proteins, which teach the immune system how to mount a two-pronged response: learning to create both the infection-fighting T-cells and B-cells.
Testing in lab animals is expected to be finished by late spring, said J. Joseph Kim, the president and CEO of Inovio. The goal is to start human tests in early summer, he said. "The virus is spreading quite rapidly," Kim said. "We believe the vaccine development has to match that speed."
