Superficially this is another example of Fauci and the federal public health bureaucracy moving the goalposts to make the pandemic more onerous for Americans but there’s real science behind the point he’s making. Watch, then read on.

Dr. Fauci says he would be "not at all be surprised" if three vaccine doses becomes the "adequate, full regimen" for protection from COVID-19 pic.twitter.com/PsQKb0gzkn

— CBS News (@CBSNews) September 2, 2021

How many shots of the mRNA vaccines does it take before someone is durably protected against severe illness?

Initially scientists thought it was two. As I understand how it works, the first dose introduces your immune system to the virus’s spike protein, generating antibodies, and the second dose boosts those antibodies while giving your body some “target practice” against the spike protein. Antibodies decline over time but it was hoped that the immune memory acquired by two exposures to the spike would allow a vaccinated person to respond quickly if and when they were exposed to the virus itself by rapidly manufacturing new antibodies to overcome it.

And that’s what happened, as even now in the age of Delta the vaccinated retain enough immune memory to fight off the virus in most cases before it spreads far enough to give them a severe case of COVID. But surging infections in Israel this summer revealed that immunity in older people waned enough after six months or so to make breakthrough infections more common, putting them at risk. It was thought that a third dose of the vaccine would not only boost their antibodies but — hopefully — produce a more durable immune memory following a third look at the spike protein.

So far, so good:

Israel: For the first time in this Delta wave, a drop in the number of severely ill hospitalized patients

675 today, down from 751 two days ago

One month after the start of the third dose campaign pic.twitter.com/RMFHyGVKqk

— Eran Segal (@segal_eran) September 1, 2021

Infection trends in Israel:

1. Infections record high, still increasing (slowly, R=1.07) – but increase only among unvaccinated (graph)

2. Booster effect (graph):
Infections in 60+ declined from 4.7 (on Aug 16) to 3.1/10k/d
Recently: 30-59 slowly declining, now 7.7/10k
Kids:⬆️ pic.twitter.com/2yE24a18fT

— Ran Balicer (@RanBalicer) September 2, 2021

Stat interviewed Stanley Plotkin, the creator of the rubella vaccine and an institution in immunology, about why three doses might be the proper regimen for the COVID vaccines instead of two:

During the meeting, Plotkin urged the ACIP to stop talking about Covid vaccine boosters. The third shot should be considered the final dose of the original series of vaccines, he argued. We may or may not need later boosters at a later date, Plotkin said. But for now, the third dose is finishing the job of generating a robust and lasting immune response.

It’s well known in vaccinology that when using inactivated or non-replicating vaccines — vaccines that don’t use a live-virus to trigger an immune response — multiple doses are needed. A priming dose (or doses) is followed four to six months later with an additional jab that helps the immune response to mature, he said. Many vaccines given in childhood are administered in a three-dose series, with a gap of several months between the second and third shots.

Does that mean the original two doses of the Pfizer and Moderna vaccines — given three and four weeks apart, respectively — were poorly timed? Plotkin, who consults with multiple vaccine manufacturers, was not ready to go there. The durability of the immune response would likely have been better had the doses been spaced out further, but going months between dose 1 and dose 2 might have led to more Covid deaths, he told STAT.

The HPV and Hepatitis B vaccines are given out in three-dose regimens for this purpose. The science is above my pay grade but spacing out doses over longer periods tends to produce stronger immune responses — including with the mRNA vaccines:

With the @Pfizer/@BioNTech_Group vaccine, significantly higher levels of receptor binding domain antibodies induced with the 8-12 week dose spacing compared with 3-6 weekshttps://t.co/P75fG7kCVR pic.twitter.com/1Yg3PYCPAl

— Eric Topol (@EricTopol) August 25, 2021

That may also explain why Moderna looks more effective than Pfizer in studies of the Delta variant. Moderna is dosed out with a four-week gap between the doses; the gap for Pfizer is just three weeks. So why didn’t scientists tell us from the start that both would be a three-dose regimen rather than two? Presumably it’s as simple as them not knowing at the time how long it would take for human immune memory to mature against a novel virus like SARS-CoV-2 after receiving a newfangled vaccine like the mRNA products. They hoped two doses would be enough. It wasn’t. Trial and error.

As for why they didn’t space out those two doses longer, they didn’t have the luxury of time. As Plotkin says, longer vaccine trials would have meant forcing the public to wait longer for a product that may have been, and actually was, effective after just three or four weeks between shots. Holding back the vaccine to test longer intervals between doses would have been fine in normal times. But during a pandemic in which thousands were dying every day, time was of the essence. They needed the shortest possible period between doses to get people “fully vaccinated” so that they’d have solid protection against severe illness. They settled on a few weeks, only to find that that didn’t generate immunity as durable as they’d hoped.

The real bummer here, of course, isn’t that three doses complicates vaccine passports in the U.S. but that it means an even longer road to getting the entire world fully vaccinated. Helping each human being gain durable immunity will now be a process of months, not weeks. Those vaccine factories will be churning for years to come.