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A booster has a solid immunological basis. The process of hypermutation and affinity maturation takes months to finish. The initial immune response to a patho

A booster has a solid immunological basis. The process of hypermutation and affinity maturation takes months to finish. The initial immune response to a pathogen is poor and takes ng/ml of antibodies to neutralize the threat. The immune system essentially has a "budget" for antibodies and the early antibodies are poor and take up too much of that. Affinity maturation produces higher affinity antibodies that are effective at pg/ml but it takes months. But you can now "fit" many more kinds of antibodies into the bloodstream. Hitting the mature immune response with a booster releases those high potency antibodies from germinal centers. This is why nearly every single vaccine we give kids comes in a series of 2 or 3 shots spaced out over 6+ months. https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolesc... https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html Very few of those are one-and-done shots. The initial mRNA shots were way too close together and were done that way out of expediency since the second shot gave a lot better protection very quickly. It also allowed the trials to complete faster and probably saved 100,000s of lives. It was basically a "wartime" decision to slam shots into arms way too fast. The increased affinity against Omicron after a booster is also something that shouldn't have been a surprise. The utility of 4th shot boosters in non-elderly non-immunocompromised and chasing after the idea of reducing spread through infection is on a lot less firm footing. Even the booster-obsessed Israelis are finding in studies that it doesn't do much good. This coronavirus also is currently mutating too rapidly and infection too many people in each wave to be able to logistically update the vaccines for new variants, so it doesn't look very useful to be thinking of it analogously to the yearly influenza shots.

kurthr 5y ago
I agree with most all of that, and that it was largely unsurprising. When the mRNA shots were developed there was a tradeoff to be made (and BNT/Mod chose slightly different paths) on both amount of RNA and dosing schedule to minimize side effects while rapidly providing strong immunity (we're also lucky JJ and they all chose a stabilized prefusion Spike unlike ChAdOx etc). Boosters for T and B response in particular are common, but orders of magnitude higher antibodies are quite likely to help minimize Omicron effects (especially for first responders who received early Pfizer doses) and do appear to cause significant reductions in infection/symptomatic cases.[1] I would not have slowed down the testing or EUA, although manufacture was an issue early on. We didn't know when/if a significantly immune evading variant would arrive, and I feel fairly lucky with when Omicron arrived (after many of the most susceptible could be vaccinated). If it had arrived 8 months earlier, it would have been catastrophic. I also feel that the WHO choices have not been very good. From down playing human transmission early in the pandemic to demanding that there not be boosters in order to speed up the multi-year process of vaccinating 4billion people by 40million doses, when Omicron was already spreading quickly. Honestly, prioritization in the developing world is more important. They seem more political than other sources. [1] https://jamanetwork.com/journals/jama/fullarticle/2788105 https://jamanetwork.com/journals/jama/fullarticle/2788105

kurthr 5y ago

I agree with most all of that, and that it was largely unsurprising. When the mRNA shots were developed there was a tradeoff to be made (and BNT/Mod chose slightly different paths) on both amount of RNA and dosing schedule to minimize side effects while rapidly providing strong immunity (we're also lucky JJ and they all chose a stabilized prefusion Spike unlike ChAdOx etc). Boosters for T and B response in particular are common, but orders of magnitude higher antibodies are quite likely to help minimize Omicron effects (especially for first responders who received early Pfizer doses) and do appear to cause significant reductions in infection/symptomatic cases.[1] I would not have slowed down the testing or EUA, although manufacture was an issue early on. We didn't know when/if a significantly immune evading variant would arrive, and I feel fairly lucky with when Omicron arrived (after many of the most susceptible could be vaccinated). If it had arrived 8 months earlier, it would have been catastrophic. I also feel that the WHO choices have not been very good. From down playing human transmission early in the pandemic to demanding that there not be boosters in order to speed up the multi-year process of vaccinating 4billion people by 40million doses, when Omicron was already spreading quickly. Honestly, prioritization in the developing world is more important. They seem more political than other sources. [1] https://jamanetwork.com/journals/jama/fullarticle/2788105 https://jamanetwork.com/journals/jama/fullarticle/2788105