What makes a vaccine's protection last?

A strong shot design might jump-start durability, but even less-than-triggering recipes aren’t doomed to fail durability tests. The how, when, how often, and how much of administration can also cement protection. Those gentle hacks are what we’re all obsessing over now, with COVID-19: how many shots we’ll need, and how far apart.

True staying power almost always requires more than one dose; most shots need to usher in multiple immunological reminders to really get the message to stick. The HPV vaccine and the measles/mumps/rubella (MMR) shot are two-dosers; the vaccines that block hepatitis B use three shots; the diphtheria/tetanus/acellular pertussis (DTaP) vaccine uses five, and that’s all before boosts. “It can make a huge difference,” Slifka said. “The immune system thinks, I must not have dedicated enough of an immune response to it the first time.” Each additional injection tends to have a nice effect on the strength of the response, pushing B and T cells to be far feistier than they were before. No clear-cut logic dictates how many refreshers a vaccine regimen will need. Some shots have added doses over the years, while others have stripped them away. Researchers around the world are still debating how often we need boosters for the shots we use to block mumps (more often?), tetanus (less often?), and yellow fever (depends whom you ask). “And every time we start to look at different pathogens, the rules can change a little bit,” UNC’s David Martinez told me.

With COVID, the math remains extra muddy, but might fit the pattern of more is more, as my colleague Rachel Gutman has written. Moderna and Pfizer are both double-dose vaccines, a one-two punch that seems to land better than J&J’s single jab. The second injections, in particular, send antibody levels soaring. The higher that early-post-vax peak crests, the more those antibodies can accomplish: They’ll be able to rally against variants they weren’t initially roused to spot. And their level will have more room and time to fall before it dips past the point of protecting against infection, disease, or death, “even if it’s decaying at the same rate,” Diane Griffin, an immunologist and measles-vaccine expert at Johns Hopkins, told me. Post-Moderna antibodies in particular surged up so high that, despite some declines, effectiveness still looks substantial, many months out; immunity-dodging variants, too, keep falling prey. The Moderna moxie might be due to how much viruslike stuff is in each dose as well. Each shot pumps in more than three times the mRNA that Pfizer’s does, perhaps scandalizing B cells into squeezing more antibodies out.