The spectacular efficacy of these vaccines, should the preliminary data hold, likely also has to do with the choice of spike protein as vaccine target. On one hand, scientists were prepared for the spike protein, thanks to research like Graham’s. On the other hand, the coronavirus’s spike protein offered an opening. Three separate components of the immune system—antibodies, helper cells, and killer T cells—all respond to the spike protein, which isn’t the case with most viruses.
In this, we were lucky. “It’s the three punches,” says Alessandro Sette. Working with Shane Crotty, his fellow immunologist at the La Jolla Institute, Sette found that COVID-19 patients whose immune systems can marshal all three responses against the spike protein tend to fare the best. The fact that most people can recover from COVID-19 was always encouraging news; it meant a vaccine simply needed to jump-start the immune system, which could then take on the virus itself. But no definitive piece of evidence existed that proved COVID-19 vaccines would be a slam dunk. “There’s nothing like a Phase 3 clinical trial,” Crotty says. “You don’t know what’s gonna happen with a vaccine until it happens, because the virus is complicated and the immune system is complicated.”
Experts anticipate that the ongoing trials will clarify still-unanswered questions about the COVID-19 vaccines. For example, Ruth Karron, the director of the Center for Immunization Research at Johns Hopkins University, asks, does the vaccine prevent only a patient’s symptoms? Or does it keep them from spreading the virus? How long will immunity last? How well does it protect the elderly, many of whom have a weaker response to the flu vaccine? So far, Pfizer has noted that its vaccine seems to protect the elderly just as well, which is good news because they are especially vulnerable to COVID-19.
Several more vaccines using the spike protein are in clinical trials too. They rely on a suite of different vaccine technologies, including weakened viruses, inactivated viruses, viral proteins, and another fairly new concept called DNA vaccines. Never before have companies tested so many different types of vaccines against the same virus, which might end up revealing something new about vaccines in general. You now have the same spike protein delivered in many different ways, Sette points out. How will the vaccines behave differently? Will they each stimulate different parts of the immune system? And which parts are best for protecting against the coronavirus? The pandemic is an opportunity to compare different types of vaccines head-on.
If the two mRNA vaccines continue to be as good as they initially seem, their success will likely crack open a whole new world of mRNA vaccines. Scientists are already testing them against currently un-vaccinable viruses such as Zika and cytomegalovirus and trying to make improved versions of existing vaccines, such as for the flu. Another possibility lies in personalized mRNA vaccines that can stimulate the immune system to fight cancer.