This news from Pfizer and Moderna is of the just-in-case variety, but there are obvious reasons why vaccinated Americans might be asked to get a third shot sometime later this year. The most obvious one is that a vaccine-resistant killer variant could pop up, instigating a scramble by pharma to produce a new product to keep it in check. That’s what Pfizer and Moderna are planning for with their new booster trials, in fact: One doctor told the Times to consider it a “test run” to see how quickly the companies can produce a new vaccine tailored to a new variant if they had to, as there’s none out there right now — even the South African one — against which the current vaccines are powerless. Their innovative mRNA technology means they can do it much faster than traditional vaccine methods can. The question is how much faster.

But there may also be some pressure from the top for people to get a third dose this fall in anticipation of another winter wave of the virus, even if there’s no threat from a new variant. It’ll depend on what sort of side effects a third dose elicits in trials and how much immunity vaccinated people still retain months after their first round of shots. If it’s true, though, that more antibodies equals better protection, then go figure that experts might end up counseling people to up their antibody titers as the weather turns colder.

The most interesting wrinkle to the booster news is that there isn’t necessarily a single strategy on how to add more protection to someone who’s already been immunized. There are three.

As concerns grow that new coronavirus variants could blunt the protective effects of vaccines, Pfizer and BioNTech said on Thursday that they planned to test a third booster shot as well as update their original vaccine…

One study will look at what kind of protection is given when people receive a third shot about six to 12 months after the initial two-dose regimen. In addition, the companies said they were speaking to regulators about testing an adapted version of the vaccine that would protect against the variant from South Africa, known as B.1.351…

Moderna, which developed a vaccine using the same technology as the Pfizer-BioNTech product, said on Wednesday that it had shipped doses of a newly adjusted vaccine to the National Institutes of Health for testing. The adapted vaccine also addresses the B.1.351 variant, which seems to dampen the effectiveness of the existing vaccines.

So, strategy one: Tweak the current vaccines so that they target a particular variant more precisely. That’s tantamount to modifying an existing weapon so that it’s more effective against a particular enemy defense.

Strategy two: Just dose people up with a third shot of the same stuff they got in shots one and two and count on the new surge of antibodies to beat back any variant they’re confronted with. “Creating a higher titer, or antibody level, is like flooding a battlefield with soldiers in the face of a fierce enemy. Eventually, the greater numbers will triumph. That, at least, is the hope,” writes Stat. Think of it as carpet-bombing a variant until there’s nothing left.

Strategy three, per Moderna’s announcement yesterday: “A multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine at the 50 µg dose level and lower.” That’s a combination of the first two strategies, adding extra antibody firepower but also including a precision weapon tailored to a particular variant. It’s also the one Scott Gottlieb seems to have in mind in this clip:

"What you want to try to do develop a protein sequence that's a consensus sequence and bakes in enough of the changes we've seen across the world that you'll have a vaccine that will be protective regardless of what the virus manages to do to itself," says @ScottGottliebMD. pic.twitter.com/VU4Zjt8chd

— Squawk Box (@SquawkCNBC) February 25, 2021

The virus will keep on mutating. Logically, a multivalent vaccine should be more effective against *potential* mutations than one that’s narrowly tailored to one particular strain.

Which strategy will work best? That’s what the trials aim to find out. For months I’ve wondered what the approval process would look like if in fact a vaccine-resistant strain emerged and began killing people in large numbers. Developing a new vaccine to meet that challenge seems to pose no real difficulty for Moderna and Pfizer’s partner, BioNTech. The challenge is whether we’d have to go through another nine-month approval process featuring lengthy phase one, two, and three trials as people die by the truckloads. The FDA finally answered that question a few days ago: No, the approval process for a modified vaccine will be much shorter. Apparently, now that we know the basic vaccines are safe, we can make certain assumptions about how safe a tweaked vaccine targeting a variant might be.

The Food and Drug Administration said on Monday that vaccine developers would not need to conduct lengthy randomized controlled trials for vaccines that have been adapted to protect against concerning coronavirus variants.

The recommendations, which call for small trials more like those required for annual flu vaccines, would greatly accelerate the review process at a time when scientists are increasingly anxious about how the variants might slow or reverse progress made against the virus…

Dr. Peter Marks, the top vaccine regulator at the F.D.A., said at the news briefing that studies would include a “few hundred” people and last several months.

How vaccine-resistant would a variant need to be for the FDA to declare that we need a new vaccine to deal with it instead of sticking with the current supply from Pfizer and Moderna? Good question. Thankfully, we’re not at that point yet. We may have that debate before the year is out.

Now, an earnest question for science-minded readers: Why is the Johnson & Johnson vaccine a one-dose product whereas Pfizer’s and Moderna’s require two doses? The big news last week was that a single dose of Pfizer’s vaccine is 85 percent effective at preventing symptomatic COVID between 15 and 28 days after receiving the shot. New data from Israel suggests that a single dose of Pfizer is 62 percent effective in preventing severe COVID and 72 percent effective in preventing death after two to three weeks. Some experts are so impressed by that level of protection that they’re questioning whether countries shouldn’t stretch their supplies of Pfizer by giving the entire population a first dose and then worrying about second doses afterward.

Recall, meanwhile, that J&J’s single-dose vaccine is 72 percent effective overall. What’s the logic, then, behind making Pfizer’s product a double-dose vaccine but J&J only a single dose? My understanding is that a second dose of Pfizer is needed because it’s uncertain how durable immunity will remain after a single dose. But shouldn’t that also be true for J&J? What is it that makes immunity from one shot of their vaccine more durable than one shot of Pfizer’s? Or is it more durable?