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Interesting, if I understand correctly this is an mRNA vaccine too, just doesn’t seem to work that well (though I continue to be amazed at how small the sample

Interesting, if I understand correctly this is an mRNA vaccine too, just doesn’t seem to work that well (though I continue to be amazed at how small the sample sizes are). What are some of the details that make two vaccines work so differently, even if they use the same underlying technology? Production quality, dosage, slight variation in the active ingredients..?

Vecr 5y ago
The other two have lots of fancy things done to the mRNA itself, including pseudouridine substitutions, 3 and 5 prime untranslated regions, and a poly-a tail. The payload comes from the NIH, and is modified by them as well with proline insertions to stabilize the spike in the prefusion form. All current EUA vaccines in the US (BioNTech, Moderna, Jansen), plus NovaVax (code not delivered to the user in that case) use some form of the NIH payload, as far as I can tell. Edit: I forgot about the proprietary mRNA delivery systems as well, I don't really know much about those.
- rich_sasha 5y ago
  Interesting list, thanks! Do you know of any popular science description of these? I did biology at middle school and not since (but I continue to find the mechanics of low-level biology fascinating).
  - vacooom 5y ago
    I found this being a very good explanation for the technically inclined: https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...
  - tobessebot 5y ago
    Should be a good start. https://berthub.eu/articles/posts/part-2-reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/part-2-reverse-engineering... https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source... https://berthub.eu/articles/posts/curevac-vaccine-and-wonders-of-biology/ https://berthub.eu/articles/posts/curevac-vaccine-and-wonder... https://berthub.eu/articles/posts/genetic-code-of-covid-19-vaccines/ https://berthub.eu/articles/posts/genetic-code-of-covid-19-v...
    - spuz 5y ago
      Thanks, these are really good reads.
  - raphlinus 5y ago
    Another good and accessible discussion of what went wrong with this vax is Derek Lowe's "In the Pipeline" blog: https://blogs.sciencemag.org/pipeline/archives/2021/06/17/curevac-comes-up-short https://blogs.sciencemag.org/pipeline/archives/2021/06/17/cu...
deleted 5y ago
[deleted]
nyokodo 5y ago
> I continue to be amazed at how small the sample sizes are ”…an interim analysis based on 134 COVID-19 cases in the study with about 40,000 volunteers in Europe and Latin America.” The sample size is 40000 is it not? That’s as big as they come.
- Gibbon1 5y ago
  You can presume that a large percentage of that 40,000 weren't exposed to covid19 during the study. I remember a year ago the Chinese shutting down a covid19 study in China because their infection rates went to zero.
  - throwaway4good 5y ago
    Could be interesting to see comparative studies of vaccines. Right now the efficacy numbers seem be affected by when and where the studies were done.
    - hannob 5y ago
      There were ideas thrown around to do one big study of various vaccines instead of multiple ones. Didn't happen, probably was too much of an organizational challenge and would've required all companies to comply to a protocol made by a third party. Scientifically it would've been the best idea. The challenge now is that the more the world gets vaccinated the harder it gets to do any meaningful trial.
      - throwaway4good 5y ago
        Why would the companies producing the vaccine have a say in this? Sure Pfizer might go “nah - we are happy with our trial - we don’t need another”. But come on ..,
        spadez 5y ago
        > Why would the companies producing the vaccine have a say in this.. Because, if I am not mistaken, these studies are funded by the companies themselves.
makomk 5y ago
For all we know it's not actually that much worse than the vaccines currently in use since those were tested before the modern variants were in circulation. (The figures for the effectiveness of the other vaccines aren't entirely comparable - they're not from controlled studies and I don't think they cover one of the latest variants that made up a reasonable proportion of infections in this trial.) I wouldn't be surprised if it's still better than the non-mRNA Johnson & Johnson vaccine too...

Vecr 5y ago

The other two have lots of fancy things done to the mRNA itself, including pseudouridine substitutions, 3 and 5 prime untranslated regions, and a poly-a tail. The payload comes from the NIH, and is modified by them as well with proline insertions to stabilize the spike in the prefusion form. All current EUA vaccines in the US (BioNTech, Moderna, Jansen), plus NovaVax (code not delivered to the user in that case) use some form of the NIH payload, as far as I can tell. Edit: I forgot about the proprietary mRNA delivery systems as well, I don't really know much about those.

rich_sasha 5y ago
Interesting list, thanks! Do you know of any popular science description of these? I did biology at middle school and not since (but I continue to find the mechanics of low-level biology fascinating).
- vacooom 5y ago
  I found this being a very good explanation for the technically inclined: https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...
- tobessebot 5y ago
  Should be a good start. https://berthub.eu/articles/posts/part-2-reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/part-2-reverse-engineering... https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source... https://berthub.eu/articles/posts/curevac-vaccine-and-wonders-of-biology/ https://berthub.eu/articles/posts/curevac-vaccine-and-wonder... https://berthub.eu/articles/posts/genetic-code-of-covid-19-vaccines/ https://berthub.eu/articles/posts/genetic-code-of-covid-19-v...
  - spuz 5y ago
    Thanks, these are really good reads.
- raphlinus 5y ago
  Another good and accessible discussion of what went wrong with this vax is Derek Lowe's "In the Pipeline" blog: https://blogs.sciencemag.org/pipeline/archives/2021/06/17/curevac-comes-up-short https://blogs.sciencemag.org/pipeline/archives/2021/06/17/cu...

deleted 5y ago

[deleted]

nyokodo 5y ago

> I continue to be amazed at how small the sample sizes are ”…an interim analysis based on 134 COVID-19 cases in the study with about 40,000 volunteers in Europe and Latin America.” The sample size is 40000 is it not? That’s as big as they come.

Gibbon1 5y ago
You can presume that a large percentage of that 40,000 weren't exposed to covid19 during the study. I remember a year ago the Chinese shutting down a covid19 study in China because their infection rates went to zero.
- throwaway4good 5y ago
  Could be interesting to see comparative studies of vaccines. Right now the efficacy numbers seem be affected by when and where the studies were done.
  - hannob 5y ago
    There were ideas thrown around to do one big study of various vaccines instead of multiple ones. Didn't happen, probably was too much of an organizational challenge and would've required all companies to comply to a protocol made by a third party. Scientifically it would've been the best idea. The challenge now is that the more the world gets vaccinated the harder it gets to do any meaningful trial.
    - throwaway4good 5y ago
      Why would the companies producing the vaccine have a say in this? Sure Pfizer might go “nah - we are happy with our trial - we don’t need another”. But come on ..,
      - spadez 5y ago
        > Why would the companies producing the vaccine have a say in this.. Because, if I am not mistaken, these studies are funded by the companies themselves.

makomk 5y ago

For all we know it's not actually that much worse than the vaccines currently in use since those were tested before the modern variants were in circulation. (The figures for the effectiveness of the other vaccines aren't entirely comparable - they're not from controlled studies and I don't think they cover one of the latest variants that made up a reasonable proportion of infections in this trial.) I wouldn't be surprised if it's still better than the non-mRNA Johnson & Johnson vaccine too...