8 ms·

Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells. Of primary importance to both viruse

Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells. Of primary importance to both viruses and our reproductive system is the membrane fusion function for instance. We must also consider how our bodies developed in the first place; “RNA world” and “virus world” theories predict our genetics evolved from RNA-based processes or even a primordial graveyard of viral RNA. We also don’t fully understand what causes autoimmune disease, but various environmental causes have been explored including bacterial and viral infections. Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus. Unfortunately the incentives in our medical system are not designed to find cures for autoimmune diseases, although they are very much incentivized for palliative care, so progress has been painfully slow in understanding the deeper complexities of the immune system.

deleted 6y ago
[deleted]
Exmoor 6y ago
> Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus. This is true. Some of the extremely rare auto-immune issues that have impacted people who have been vaccinated for specific flu viruses in, IIRC, 1976 and 2009, were thought to occur at even higher rates and severity with people who contracted the virus. So, vaccination might impact you, but likely worse the the virus itself due to the greater amount of virus in your system. I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.
- programmarchy 6y ago
  Yeah, I’m actually very hopeful that mRNA medicine will be able to overcome issues like these in ways traditional vaccines couldn’t. For example, variations could be developed that are more effective for each racial group, rather than a one-size-fits all approach that may be biased. From there, perhaps even individuals who have autoimmune disease markers could have variants developed for them as well.
  - axiosgunnar 6y ago
    Are you saying there are genetic differences between races?
    - mschuster91 6y ago
      Yes, certain medications have different dosages depending on ethnic groups: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.107.704023 https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.... There exist even special medicine to account for genetic differences in Black people: https://en.wikipedia.org/wiki/Isosorbide_dinitrate/hydralazine https://en.wikipedia.org/wiki/Isosorbide_dinitrate/hydralazi...
    - jcims 6y ago
      There are definitely phenotypical variations in humans that have health implications. To the extent that some of these are adaptive to region they may align with the rather poorly defined buckets we call ‘race’. To GP’s point, lack of diversity in clinical trials can result in medicines that vary in efficacy and safety in the broader population. The ability to customize a therapy to an individual would help reduce the impact of this issue.
    - panta 6y ago
      AFAIK there are no human races from a taxonomic point of view, all human beings belong to the same subspecies. There are of course genetic differences between individuals and ethnic groups though, otherwise we would be all identical twins (the point is not condemning the differences - differences are in general a good thing - the point is not attaching value judgements to the differences).
      - rory 6y ago
        Subspecies definitions can be rather arbitrary in general, and don't fit well to a species with the technology of humans. 1000 years ago you probably could have said that indigenous subsaharan Africans and Americans are different subspecies of homo sapiens simply because one group has darker brown skin and lives in Africa, and one has lighter brown skin and lives in the Americas (phenotype difference + range difference is all it takes). But today the "native range" of every ethnic group is essentially global due to airplanes and immigration, so you'd probably say we're all one subspecies. But either way, the label "subspecies" conveys far less information than people sometimes assign it.
- jcims 6y ago
  >I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus. This is the angle that, for me, is suppressing my innate concern for a widescale and rapid application of a brand new immunological therapy. It's extremely targeted and feels like the future. I can imagine a day where the FDA approves the process rather than the instance of mRNA-based therapies, allowing for highly personalized treatment.
  - prox 6y ago
    I believe this is one of the reason a Harvard Professor was pushing for a 3 month extended phase 3/4 trial. This was recently noted in a AMA by virus experts on reddit.
Turing_Machine 6y ago
> Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells. Sure, but aren't the proteins produced by the vaccine virtually identical to the ones produced by the actual virus? If so, the calculus looks like this: 1) Take the vaccine and accept the (unknown, but apparently quite small) probability that something in your body will react very negatively to the generated viral proteins. 2) Get the virus, accept the probability (also unknown, but the same as in 1) that something in your body will react very negatively to the viral proteins, plus accept the additional risk of being infected by the actual virus. I guess the third possibility would be to refuse the vaccine and gamble that you won't get the virus, either.
- antonzabirko 6y ago
  Or have the virus already and get immunity in that way.
  - Turing_Machine 6y ago
    That would be the same as 2, in terms of risk from the body reacting negatively to the viral proteins.
  - serpix 6y ago
    and possibly infect scores of other people, some of them not so lucky and will get the serious case requiring hospitalisation or worse.
    - programmarchy 6y ago
      It’s not clear if the vaccine will prevent infectiousness yet, unfortunately, so for now it’s best to assume even vaccinated people can spread the virus until more is known. Both ways will increase herd immunity.
- jcims 6y ago
  I generally agree with you. Keep in mind I'm at 'stayed at the Holiday Inn' levels of competence here, but in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus. This could be incorrect. If that's generally true, the difference here would be that the part of the spike protein topology that is typically bound to other proteins in an actual infection would be accessible to the immune system in the case of a vaccination. I think that is where the differential risk could occur with a vaccination that wouldn't occur with an actual infection (however small that might be). In my daughter's case, something happened when she was about 14 years old that caused her body to determine that the beta cells in her pancreas were invaders and have to die, so I'm just tuned into this kind of possible side effect.

deleted 6y ago

[deleted]

Exmoor 6y ago

> Presumably if a viral infection could trigger an autoimmune response in certain genetically predisposed groups, then so could a vaccine designed to mimic a virus. This is true. Some of the extremely rare auto-immune issues that have impacted people who have been vaccinated for specific flu viruses in, IIRC, 1976 and 2009, were thought to occur at even higher rates and severity with people who contracted the virus. So, vaccination might impact you, but likely worse the the virus itself due to the greater amount of virus in your system. I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus.

programmarchy 6y ago
Yeah, I’m actually very hopeful that mRNA medicine will be able to overcome issues like these in ways traditional vaccines couldn’t. For example, variations could be developed that are more effective for each racial group, rather than a one-size-fits all approach that may be biased. From there, perhaps even individuals who have autoimmune disease markers could have variants developed for them as well.
- axiosgunnar 6y ago
  Are you saying there are genetic differences between races?
  - mschuster91 6y ago
    Yes, certain medications have different dosages depending on ethnic groups: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.107.704023 https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.... There exist even special medicine to account for genetic differences in Black people: https://en.wikipedia.org/wiki/Isosorbide_dinitrate/hydralazine https://en.wikipedia.org/wiki/Isosorbide_dinitrate/hydralazi...
  - jcims 6y ago
    There are definitely phenotypical variations in humans that have health implications. To the extent that some of these are adaptive to region they may align with the rather poorly defined buckets we call ‘race’. To GP’s point, lack of diversity in clinical trials can result in medicines that vary in efficacy and safety in the broader population. The ability to customize a therapy to an individual would help reduce the impact of this issue.
  - panta 6y ago
    AFAIK there are no human races from a taxonomic point of view, all human beings belong to the same subspecies. There are of course genetic differences between individuals and ethnic groups though, otherwise we would be all identical twins (the point is not condemning the differences - differences are in general a good thing - the point is not attaching value judgements to the differences).
    - rory 6y ago
      Subspecies definitions can be rather arbitrary in general, and don't fit well to a species with the technology of humans. 1000 years ago you probably could have said that indigenous subsaharan Africans and Americans are different subspecies of homo sapiens simply because one group has darker brown skin and lives in Africa, and one has lighter brown skin and lives in the Americas (phenotype difference + range difference is all it takes). But today the "native range" of every ethnic group is essentially global due to airplanes and immigration, so you'd probably say we're all one subspecies. But either way, the label "subspecies" conveys far less information than people sometimes assign it.
jcims 6y ago
>I am not a scientist, but I would expect that the mRNA vaccines would have less of a chance of having an auto-immune reaction since they contain only one of the many proteins contained in the actual virus. This is the angle that, for me, is suppressing my innate concern for a widescale and rapid application of a brand new immunological therapy. It's extremely targeted and feels like the future. I can imagine a day where the FDA approves the process rather than the instance of mRNA-based therapies, allowing for highly personalized treatment.
- prox 6y ago
  I believe this is one of the reason a Harvard Professor was pushing for a 3 month extended phase 3/4 trial. This was recently noted in a AMA by virus experts on reddit.

Turing_Machine 6y ago

> Do we really know this? Obviously the spike proteins are using an existing mechanism (ACE2) in our bodies to bind to cells. Sure, but aren't the proteins produced by the vaccine virtually identical to the ones produced by the actual virus? If so, the calculus looks like this: 1) Take the vaccine and accept the (unknown, but apparently quite small) probability that something in your body will react very negatively to the generated viral proteins. 2) Get the virus, accept the probability (also unknown, but the same as in 1) that something in your body will react very negatively to the viral proteins, plus accept the additional risk of being infected by the actual virus. I guess the third possibility would be to refuse the vaccine and gamble that you won't get the virus, either.

antonzabirko 6y ago
Or have the virus already and get immunity in that way.
- Turing_Machine 6y ago
  That would be the same as 2, in terms of risk from the body reacting negatively to the viral proteins.
- serpix 6y ago
  and possibly infect scores of other people, some of them not so lucky and will get the serious case requiring hospitalisation or worse.
  - programmarchy 6y ago
    It’s not clear if the vaccine will prevent infectiousness yet, unfortunately, so for now it’s best to assume even vaccinated people can spread the virus until more is known. Both ways will increase herd immunity.
jcims 6y ago
I generally agree with you. Keep in mind I'm at 'stayed at the Holiday Inn' levels of competence here, but in my mind the spike proteins that are generated by an actual infection don't typically leave the cytoplasm detached from the rest of the virus. This could be incorrect. If that's generally true, the difference here would be that the part of the spike protein topology that is typically bound to other proteins in an actual infection would be accessible to the immune system in the case of a vaccination. I think that is where the differential risk could occur with a vaccination that wouldn't occur with an actual infection (however small that might be). In my daughter's case, something happened when she was about 14 years old that caused her body to determine that the beta cells in her pancreas were invaders and have to die, so I'm just tuned into this kind of possible side effect.