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Kept meaning to do this thread on the duration of vaccine immunity, but got paralyzed b/c of length. So instead I'll break it up into 3 pieces, becoming increasingly geekier and wonkier. TLDR, I think it's likely that vaccine immunity against symptomatic disease will be >1yr.
I’ll focus only on antibodies, as the thread is long enough as is even w/o memory cells. Today, I’ll speculate on antibody levels that are protective. In part 2 later next wk, I’ll talk about the cell biology/immunology, and then in part 3 I’ll try to link the mechanisms of the
vaccines back to the cell biology and predictions on durability.
Based on a lot of metrics, it doesn’t seem to take much to protect against symptomatic disease (preventing all infections will be harder as per this article by @apoorva_nyc https://www.nytimes.com/2020/12/08/health/covid-vaccine-mask.html).
Based on a lot of metrics, it doesn’t seem to take much to protect against symptomatic disease (preventing all infections will be harder as per this article by @apoorva_nyc https://www.nytimes.com/2020/12/08/health/covid-vaccine-mask.html).
That is good re:duration of immunity, as you can decline a lot and still remain protected. This nice Dan Barouch paper showed that passive transfer of antibodies into macaques was protective. https://www.nature.com/articles/s41586-020-03041-6
The required nAb titer for protection was only ~50 for a dose of ~100,000 viruses, which is likely more than the natural inoculum. nAb assays differ across labs, but it does seem that the vaccines routinely induce Ab levels that are higher than this. https://www.nature.com/articles/s41586-020-2798-3/tables/2
Tangent: this study estimates the natural inoculum at only a few thousand infectious viruses. https://stm.sciencemag.org/content/12/573/eabe2555 Other estimates using different methods have landed in the same ballpark. https://www.medrxiv.org/content/10.1101/2020.10.21.20216895v1 H/t @dylanhmorris
Couple that with studies that estimate the rate of symptomatic re-infection to be very low. This despite huge variation across people in the magnitude of the immune response. Many people mount wimpy responses, yet it still seems to be protective. https://www.medrxiv.org/content/10.1101/2020.11.18.20234369v1
The highest profile recent evidence came from Pfizer’s first dose. There appears to be protection after ~10 days. Based on their phase 2 data, the mean nAb titers at this point are only ~15. That’s pretty low. https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
Compare that to something super-contagious like measles, where we think we need nAb levels >100 to protect against symptoms, and maybe >1000 to protect against all infections. https://pubmed.ncbi.nlm.nih.gov/2230231/
After the second Pfizer dose, the nAb titers go up 10-20-fold ( https://www.nejm.org/doi/full/10.1056/NEJMoa2027906). That leaves a lot of room for decline while still maintaining protection. Even if every antibody-producing cell died en masse, all at once, the
half-life of IgG alone would keep you immune for months. But of course this mass extinction doesn't happen in this way (part 2 sometime next week). In fact, the Moderna titers through 4 months at least look pretty good: https://www.nejm.org/doi/full/10.1056/NEJMc2032195
Put it all together, and I would be surprised if, in the typical Pfizer/Moderna vaccine response, antibodies fell below the protective threshold in <1 year. For the others where we have less data, I'll speculate more based on the cell biology in part 2 prob. next week.
