A follow-up to Jazz’s post yesterday about the surprising new study showing Moderna is considerably better at preventing infection by Delta than Pfizer is, although both vaccines remain very good at preventing severe illness. That was a surprise because they rely on the same mRNA technology and have shown similar effectiveness against prior variants. Why would Delta be different?

Maybe it isn’t, says Scott Gottlieb. Maybe the reason Pfizer is weaker against Delta than Moderna has less to do with the vaccine itself than when it was administered and to whom it was administered.

Be warned that Gottlieb has a financial incentive to say that. I think he’s a straight shooter on public-health matters but he happens to sit on the board of Pfizer. It wouldn’t be good for his company to have Americans rushing to get Moderna.

"I've long said I think these two mRNA vaccines are comparable in terms of their efficacy," says @ScottGottliebMD. "Pfizer vaccine was distributed earlier and was also distributed to people who might be at more risk of either contracting COVID or coming into contact with COVID." pic.twitter.com/KQtOaEOHU6

— Squawk Box (@SquawkCNBC) August 12, 2021

Does that explain it? Pfizer was given a little earlier than Moderna was and it was given to people with weaker immune systems (nursing-home residents) or with high exposure to infectious COVID patients (medical personnel). Go figure that immunity would fade sooner in vulnerable people who got the shot earlier than Moderna recipients did.

A question, though. Since doctors and nurses are routinely in contact with people with COVID, wouldn’t we expect them to be more immune than the average vaccinated joe at this point? Many of them must have been infected between the time of their vaccination and Delta’s arrival. Those infections presumably generated antibodies, giving them an immunity boost. If anything, that “invisible” booster shot should make Pfizer recipients within the health-care profession more protected now than random Moderna recipients are, no?

Either way, I’m intrigued by the theory that Pfizer is doing worse against Delta than Moderna mainly because of when it was given, not because of some inherent deficiency in the vaccine. There’s evidence from Israel, where everyone received Pfizer, that immunity has waned over time:

This vulnerability to infections appears to be driven by time since vaccine, such as seen in this Israeli analysis. The age trend is noted, not statistically significant https://t.co/Oh8nRRAtjA pic.twitter.com/ylFiRTyRpg

— Eric Topol (@EricTopol) August 12, 2021

Among the 60+ age group there, people who were vaccinated more than 146 days before the time of the study were around three times as likely to have a breakthrough infection as people in the same group who were immunized less than 146 days before. Hmmmm.

Here’s the cheat-sheet breakdown of studies comparing how the two mRNA vaccines hold up against Delta. Note the one from Qatar:

There are now 5 mRNA vaccine effectiveness studies for preventing Delta infections, and more on the way. Except for @PHE_UK, all show a marked reduction, particularly for @Pfizer, but the @moderna_tx comparison is confounded by its later administration (less chance to see waning) pic.twitter.com/lKzR1UvOpl

— Eric Topol (@EricTopol) August 12, 2021

Qatar had Pfizer vaccines in hand by late December of last year but Moderna wasn’t approved for emergency use in that country until mid-February. Did Pfizer recipients there do worse against Delta than Moderna recipients because Pfizer isn’t as effective, or did they do worse because they received their shots earlier on average and their immunity had already begun to wane when the study was conducted? Hmmmm.

There’s one more difference between Pfizer and Moderna unrelated to the substance of the vaccines that may explain why the latter performs better against Delta, and again it has to do with time. The time between the first and second doses of Pfizer is typically three weeks; the time between the first and second doses of Moderna is four weeks. Does that extra week matter? Maybe. A UK study published last month found that delaying the second dose induces the body to generate more antibodies once that dose is finally given. The “sweet spot” for Pfizer against Delta, according to the researchers, was eight weeks between doses, not three. Maybe having to wait an extra week for their second dose was a blessing in disguise for Moderna recipients, boosting their immune system meaningfully beyond what a three-week interim would have.

And maybe the UK finding explains why that country has done so much better with its summer Delta wave than we have. Remember that the UK followed a “first doses first” strategy that ignored the recommended three-week interval for Pfizer doses. The British government believed they’d slow the spread of the virus more efficiently by generating partial immunity in a large share of the population than by generating full immunity in a smaller share. The available vaccine supply was used to give everyone a first dose and only once that was done, months later, did second doses start going out. That had two benefits. By delaying the second dose, the Brits got closer to the immunity interval “sweet spot” than we did. And by giving out many of their second doses later in the year than we in the U.S. did, they fortuitously boosted the immunity of a huge share of their population right before Delta arrived.

Put simply, population-wide immunity may have waned to a much lesser extent in the UK at the moment than it has here. Result: Hospitalizations during their current Delta wave have (so far) topped out at around a quarter of what they were at the winter peak. In the U.S., hospitalizations are now at around half of what they were at the peak and are still rising.

If in fact our wave is a function of waning immunity more so than weaker vaccine protection against Delta, the case for boosters — soon — is clear.

I’ll leave you with this reminder that the vaccines are still doing their most important job, keeping people out of the hospital. Immunity may have waned but it hasn’t disappeared.

The diagnosis and denial of waning immunity from Delta infections (*does not pertain to hospitalizations or deaths*)
In July, @IsraelMOH issued a report that showed a marked decline in mRNA vaccine (@Pfizer) protection vs Delta infections, down to 40%. That was met with disbelief pic.twitter.com/IUT5QMsd6G

— Eric Topol (@EricTopol) August 12, 2021