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Comment by angelzen | Hacker News Reader

Nuance: Touting high effectiveness agains infection, which degrades over time. This has been explained elsewhere in this thread, the original vaccine claims were similar and later morphed into "but the vaccine was always designed to protect against severe infection".

Nuance: Not mentioning that their own full application estimates saving one in a million children, under the best circumstances. See Table 14 on page 34.

The difficult ethical question: on one hand there is 1 child you may save given the information available today. On the other hand you don't know which one ahead of time, you need to inoculate 1 million children with a vaccine for which you don't have any longterm data on.

https://www.fda.gov/media/153447/download

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Ok, let's have a look what the vaccine manufacturers claimed in their phase 3 study papers about the durability of the protection:

BioNTech/Pfizer [1]: "This report includes 2 months of follow-up after the second dose of vaccine for half the trial participants and up to 14 weeks’ maximum follow-up for a smaller subset. Therefore, both the occurrence of adverse events more than 2 to 3.5 months after the second dose and more comprehensive information on the duration of protection remain to be determined."

Moderna [2]: "Another limitation is the lack of an identified correlate of protection, a critical tool for future bridging studies. As of the data cutoff, 11 cases of Covid-19 had occurred in the mRNA-1273 group, a finding that limits our ability to detect a correlate of protection. As cases accrue and immunity wanes, it may become possible to determine such a correlate."

AstraZeneca [3]: "In this interim analysis, we have not been able to assess duration of protection, since the first trials were initiated in April, 2020, such that all disease episodes have accrued within 6 months of the first dose being administered. Further evidence will be required to determine duration of protection and the need for additional booster doses of vaccine."

Johnson & Johnson [4]: "A limitation of the trial is the relatively short follow-up, which was necessitated, as in other Covid-19 vaccine trials, by the urgent need for vaccine. The data do not suggest a waning of protection."

[1] https://www.nejm.org/doi/full/10.1056/nejmoa2034577 [2] https://www.nejm.org/doi/full/10.1056/nejmoa2035389 [3] https://www.thelancet.com/journals/lancet/article/PIIS0140-6... [4] https://www.nejm.org/doi/full/10.1056/NEJMoa2101544

Speaking of protection (vaccine effectiveness against infection) durability, I have to admit there is a certain level of disappointment seeing charts like Figure 1 in a US veteran study, which flat out contradicts the J&J claims (VEaI 3%) and partly invalidates the Pfizer claims (VEaI 56%). Or a Qatar study. Or a Sweden study.

There is also the official reaction. Aug 18, 2021: "CDC Director Says Coronavirus Vaccines Less Effective For Delta But Still Prevent Severe Infection".

Possible all of these studies are flawed. And perhaps I'm accidentally misquoting Rachel Walensky. Given that the original trials were closed by vaccinating the control arm of the studies, not even sure where to look for credible longterm tracking of VE against infection data.

On the other hand, possibly the manufacturer original studies were flawed. Or the virus evolved, Delta, duh. These conversations are difficult to carry partly because we are supposed to take the original studies, created with (acceptable) conflict of interest as gold standard, and summarily dismiss any independent verification thereof.

https://www.medrxiv.org/content/10.1101/2021.10.13.21264966v...

https://www.nejm.org/doi/full/10.1056/NEJMoa2114114

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3949410

https://www.forbes.com/sites/andrewsolender/2021/08/18/cdc-d...

PS. One more recent VE study picked from the comments, https://www.nature.com/articles/s41591-021-01548-7/tables/3

UK, VE vs delta over 90 days

  days  VEaPCRI  VEaSI
  after
  2nd
  dose

  14    85%      93%
  30    83%      92%
  60    80%      86%
  90    75%      78%

The trend makes me fairly intrigued to see the follow up at 180, 270 etc. days after 2nd dose.

Watch this till the end : https://www.youtube.com/watch?v=TSZMtSPX3iE

To be fair, before we get carried away, VE against severe infection persists much better given the limited data we have and considering the in-the-field hospitalization & death rates. For adults, especially older, the vaccine is a big net positive.

I don't get what point you are trying to make. Yes, the vaccine efficacy drops over time. This is expected since the antibody levels in the blood drop over time. The manufacturers have pointed out from the beginning that this drop and the potential need for a third shot have to be determined from real-world data, as was done in many studies.

Now the picture seems to be that vaccine effectiveness does indeed drop over time, but protection against severe disease remains pretty strong, with the possible exception of old people who tend to have a weak immune response. Most governments have reacted by recommending third shots to this group in order to further improve the protection.

I really can't see any controversy here. This is precisely the procedure one expects when a new vaccine is introduced.

It is also worth pointing out, that even without boosters the vaccines vastly outperform any medication tested against COVID so far. And they do that much cheaper and with lower side effects.

"Yes, the vaccine efficacy drops over time." That's it. Pfizer made their core of their argument to FDA for 5-11 age group based on VE against infection numbers that we agree do not hold over time. They should take their time to conduct a real study and demonstrate real clinical benefits. There is no rush.

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