Read on Twitter
This article is not too bad in the grand scheme of things, but I admit I had a visceral reaction to the headline--'Not this again!' h/t @KurtadikarKetan. There are important points in the article itself--re: durability of Ab production in older folks... https://www.forbes.com/sites/williamhaseltine/2020/12/22/the-moderna-vaccines-antibodies-may-not-last-as-long-as-we-hoped/?sh=6c5578ce4567
but it also veers close to more problematic takes. As a reminder, despite some panic at the beginning re: waning antibodies post-infection, many studies (including ours) have found nothing particularly unusually transient. Many more recent studies too. https://twitter.com/deeptabhattacha/status/1316137615976873984
So in hopes of not having to re-litigate this yet again later, I'm going to go into the geeky cell biology of Ab production. TLDR--you *cannot* extrapolate the duration of immunity from the early decline phase of the Ab response.
If you do, you'll often underestimate the duration of immunity. At the heart of the issue are these beautiful plasma cells. Our lab is promiscuous with the viruses we use (or even *gasp* bacteria @mraffatellu @KatRhds), but we always come back around to plasma cells
Plasma cell produce 1000s of Abs/second--they are true antibody factories. Early after vaccination or infection, tons of plasma cells are made, but they don't live for long and they produce Abs that don't stick that well. But at the same time, there is an intense competition in
germinal centers for cells that make better Abs. As the quality of the Abs improves, so too does the lifespan of plasma cells that produce them. Although many fewer plasma cells are made later, you don't take a proportional loss in protection b/c the Abs are better.
How long does a typical long-lived plasma cell live? This super-cool study used carbon-14 dating to estimate an average lifespan of decades. https://rupress.org/jem/article/214/2/309/42325/Antibody-secreting-plasma-cells-persist-for
So a stereotypical response would look something like this (from our review/perspective w/ @nbaumgarth https://www.jimmunol.org/content/205/9/2342.long). If you try to extrapolate from that initial decline, you will likely underestimate the duration of immunity.
But the duration of antibody production varies a lot with the infection or vaccine. This groundbreaking study by @MarkSlifka demonstrates the point. Incidentally, it was his early work that taught me abt these cells. Give him a follow if you don't already! https://www.nejm.org/doi/full/10.1056/NEJMoa066092
Are there shortcuts to predicting how long antibodies will be produced? Unfortunately no, not with any precision. Long- and short-lived plasma cells look very similar wrt the genes they turn on--a major source of frustration for the lab https://www.sciencedirect.com/science/article/pii/S2211124718312026?via%3Dihub
Of the few differences, not many are conserved across species. We've observed changes in how they use nutrients like glucose and amino acids, but these properties are not sufficient for us to take a blood sample and tell you how long you will be immune. https://www.sciencedirect.com/science/article/pii/S107476131630214X?via%3Dihub
There are *some* general guidelines of vaccines that correlate with durable antibody immunity, reviewed by @MarkSlifka. Based on these criteria, I think Novavax looks really good (no surprise to those who follow me), but more on that later. https://www.frontiersin.org/articles/10.3389/fimmu.2019.00956/full
But back to the Moderna data. Is there any particular reason to be worried? No, not really, but it is important to follow this over time. It *might* be the case that Ab production is short-lived in the elderly, but nothing in the data yet shows that it will be.
