The way the Covid-19 crisis ends is with vaccines—not a vaccine. More than one horse can win this race. Some of us might end up getting a shot of a more traditional vaccine, which uses parts of an inactivated virus to stimulate immunity. Others might get vaccines based on emerging technologies that use synthetic versions of the virus’s genetic code.
One such novel candidate, based on RNA and made by Moderna, showed promising results in early human trials, though critics warned the evidence is preliminary. Meanwhile, a different prototype based on DNA made headlines for an experiment that showed it worked in monkeys.
In the end, some vaccines might be extremely effective but harder to scale; others the opposite. Even a less-effective vaccine might work well enough to provide herd immunity in a wider population. Other vaccines might be more appropriate for health care workers, who have to risk exposure on the job, and need protection as soon as possible.
Scientists have created more than 70 vaccine candidates so far. “If we end up with two, three, or four vaccines, that’s good, since we have seven billion people,” says Harvard vaccine researcher Dan Barouch, who led the development of one of the vaccines featured in recent news. His group began working on a vaccine in January, after the virus started spreading in China.
There are good reasons for him and other scientists to be optimistic. “For Covid-19, it’s clear most humans who get infected recover … that alone shows the human immune system can eliminate the virus,” he says. That makes it a much easier target than HIV, which he calls unprecedented in the history of vaccinology for its ability to evade the immune system. And the SARS-Cov2 virus doesn’t have the fast mutation rate that makes flu viruses a moving target.
Art Krieg, a physician and founder of Checkmate Pharmaceuticals, says he’s very optimistic that because the human immune system can successfully battle the virus, so will one or more of the many experimental vaccines.
All vaccines have to provide a danger signal to “prime” the immune system into acting against an invader. In 1995, Krieg reported the discovery one of these danger signals—called CpG DNA—which has been used in several vaccines, including one for hepatitis B, and is in some of the experimental candidates against the virus that causes Covid-19.
Next, the vaccine has to mimic the invader in order to get the immune system to create specific antibodies that target the intended enemy. Vaccine designers using genetic material (DNA or RNA) have to stimulate the immune system enough to generate those antibodies, but not so much that the immune system destroys the vaccine before it can complete its mission.
The biggest driver of recent headlines (and stock market drama) was a vaccine produced by the Massachusetts-based company Moderna, which is based on synthetic genetic material identical to parts of the code carried by the coronavirus. The genetic material is RNA—the single-stranded cousin of DNA. (Other RNA vaccines are being studied by BionTech, Translate Bio, and Curevac.) The RNA tricks human cells into making proteins identical to the “spike” proteins the virus uses to penetrate human cells. And that, in turn, stimulates the immune system to make antibodies that will be ready to block that protein if the real coronavirus invades.
The excitement about Moderna’s vaccine followed the release of data from a trial that involved 45 volunteers, though the company only described results for eight of them. Of the eight, all produced antibodies with the desired “neutralizing” property needed to attack the virus in the future. What happened to the other 37 people? Since this vaccine requires two doses, they probably just didn’t have that data yet, says Krieg.