3 ms·

The main issue IMO is that the original dose schedule of 2 doses 1 month apart is stupid, goes against pretty much all of our first principles understanding of

The main issue IMO is that the original dose schedule of 2 doses 1 month apart is stupid, goes against pretty much all of our first principles understanding of immunology, and was driven by a regulatory need for a short time window for testing/deployment (it’s quicker to test a vaccine w 1 month window than one with 6 month window), not due to science. The optimal dosing schedule is more likely to be once mRNA vaccine and a second one 6 months later. Source: family member is a chief scientist at a few drug discovery startups. Most people will have a durable immune response with the schedule above.

lamontcg 5y ago
No, the second dose greatly increases the efficacy against hospitalization and death in the short term. It wasn't "stupid" or "not due to science". It optimized for maximum vaccine efficacy at around the 5 week timepoint. Canada took a slightly longer dosing schedule to get more people their first doses faster due to having less available doses. But they didn't go with a 6 month interval either, and there's a difficult calculus there where it isn't at all obvious that one choice is "stupid". With Delta slamming into India and a lot of doses available in the USA the short schedule got the bulk of the population as immunized as possible. There's a whole lot of hindsight bias going in trying to claim that was just dumb or unscientific. It probably did save some lives in the summer of 2021 because we did have the doses in this country. Someone who got vaccinated in early April would have only been getting boosted then in early Oct 2021 and that would have been after 75% of the Delta wave had already passed. Second doses clearly needed to be going into arms sooner than 6 months and you can only figure out what timing might have been in optimal in retrospect when you know what the virus was going to do. It is correct that it didn't allow time for the immune response to mature before the boost and that is the rationale for the third shot. And for anyone getting vaccinated now, particularly young people a 6 month schedule of 2 doses may make more sense (although you always have to look at that 6 month interval and do the calculation on what the risk is of getting COVID during that interval -- at this point though presumably a person who isn't vaccinated isn't very concerned about that and probably has already been exposed at some point).
- 0xB31B1B 5y ago
  The benefit of 1 shot is very high for the first 6 months, it prevents the large majority of hospitalizations and deaths, but it does not prevent transmission. The decision to have a 1 month period between doses was determined by "time to market" not the ideal dosing schedule. Had drug makers tried to optimize for the ideal dosing schedule, then we would have had 6 more months of deaths while we waited for result which was a negative outcome. Now that the drugs are on the market, and we have sufficient evidence without running an additional stage 2 and 3 trial, the FDA should change guidance to suggest 2nd dose at 6 months instead of 1 month for people who aren't at high risk.
  - lamontcg 5y ago
    Those are all much more reasonable statements now that you've backed off from calling it unscientific stupidity.

lamontcg 5y ago

No, the second dose greatly increases the efficacy against hospitalization and death in the short term. It wasn't "stupid" or "not due to science". It optimized for maximum vaccine efficacy at around the 5 week timepoint. Canada took a slightly longer dosing schedule to get more people their first doses faster due to having less available doses. But they didn't go with a 6 month interval either, and there's a difficult calculus there where it isn't at all obvious that one choice is "stupid". With Delta slamming into India and a lot of doses available in the USA the short schedule got the bulk of the population as immunized as possible. There's a whole lot of hindsight bias going in trying to claim that was just dumb or unscientific. It probably did save some lives in the summer of 2021 because we did have the doses in this country. Someone who got vaccinated in early April would have only been getting boosted then in early Oct 2021 and that would have been after 75% of the Delta wave had already passed. Second doses clearly needed to be going into arms sooner than 6 months and you can only figure out what timing might have been in optimal in retrospect when you know what the virus was going to do. It is correct that it didn't allow time for the immune response to mature before the boost and that is the rationale for the third shot. And for anyone getting vaccinated now, particularly young people a 6 month schedule of 2 doses may make more sense (although you always have to look at that 6 month interval and do the calculation on what the risk is of getting COVID during that interval -- at this point though presumably a person who isn't vaccinated isn't very concerned about that and probably has already been exposed at some point).

0xB31B1B 5y ago
The benefit of 1 shot is very high for the first 6 months, it prevents the large majority of hospitalizations and deaths, but it does not prevent transmission. The decision to have a 1 month period between doses was determined by "time to market" not the ideal dosing schedule. Had drug makers tried to optimize for the ideal dosing schedule, then we would have had 6 more months of deaths while we waited for result which was a negative outcome. Now that the drugs are on the market, and we have sufficient evidence without running an additional stage 2 and 3 trial, the FDA should change guidance to suggest 2nd dose at 6 months instead of 1 month for people who aren't at high risk.
- lamontcg 5y ago
  Those are all much more reasonable statements now that you've backed off from calling it unscientific stupidity.