4 ms·

Can anyone speak to these nanoparticles and why this technique hasn't been seen before? Maybe more generally why we haven't targeted this part of the virus that

Can anyone speak to these nanoparticles and why this technique hasn't been seen before? Maybe more generally why we haven't targeted this part of the virus that doesnt change?

Moto7451 4y ago
This is all state of the art research. It’s the same reason we didn’t have mRNA vaccines 10 years ago.
- BitwiseFool 4y ago
  And from what I understand, mRNA vaccine technology was languishing before the urgency of Covid put their development into overdrive.
  - origin_path 4y ago
    It wasn't languishing, that word implies people knew about it but weren't paying attention or trying to make it work. mRNA based drugs hadn't launched because repeat dosings created serious side effects, as the body seemed to start reacting to the lipid capsule. From an article in 2017: https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ "for its chemists, those [lipid] nanoparticles created a daunting challenge: Dose too little, and you don’t get enough enzyme to affect the disease; dose too much, and the drug is too toxic for patients." "the Crigler-Najjar treatment has been indefinitely delayed, an Alexion spokeswoman told STAT. It never proved safe enough to test in humans, according to several former Moderna employees and collaborators who worked closely on the project. Unable to press forward with that technology, Moderna has had to focus instead on developing a handful of vaccines" Note the following paragraphs: "mRNA is a tricky technology. Several major pharmaceutical companies have tried and abandoned the idea, struggling to get mRNA into cells without triggering nasty side effects [snip] The indefinite delay on the Crigler-Najjar project signals persistent and troubling safety concerns for any mRNA treatment that needs to be delivered in multiple doses, covering almost everything that isn’t a vaccine" In 2017 mRNA was considered "tricky" and with "nasty side effects". It was considered safe for vaccines by Moderna only because, they claimed, vaccines don't require repeat doses. This is surprising given that some countries now want to make mRNA vaccination a regular yearly event. The reason they didn't focus on vaccines originally is related to that belief - vaccines are traditionally something you take once and are then protected for decades or for life. They are cheap and often bought by governments that demand bulk discounts, thus they are poor business compared to drugs that may require you to take them every week.
    - hahaitsfunny 4y ago
sterlind 4y ago
We didn't know what part of the virus would change before the virus started changing. A small number of patients developed broadly-neutralizing antibodies (bnABs), which not only wiped out Covid classic, but kept working well against the other variants too. Once we found out what part of the spike protein those antibodies bound to, then we knew what to target. But it's still not easy to raise antibodies to recognize specific sites on a protein - the more "context" you include, the more likely it is that your immune system will find another, less effective, handle on the protein to grab and call it a day. I suppose we knew about pan-coronavirus conserved sites before, but it (imo) would have been too risky to try targeting those sites with the first mRNA vaccines - one experimental technology at a time.
- ch4s3 4y ago
  If targeting pan-coronavirus conserved sites works out, it will be big news for other vaccines in the future.
sp332 4y ago
Each nanoparticle holds 20 antigens next to each other. The researchers say this provides a stronger signal to the immune system that there is a danger. https://www.niaid.nih.gov/news-events/nanoparticle-flu-vaccine https://www.niaid.nih.gov/news-events/nanoparticle-flu-vacci...
mikepurvis 4y ago
Without really knowing the first thing about it, I'm curious if the nanoparticles discussed here are the same or similar to the "virus-like particles" that Medicago describes as being the key to their vaccine technology: https://medicago.com/en/our-technologies/virus-like-particles/ https://medicago.com/en/our-technologies/virus-like-particle... https://en.wikipedia.org/wiki/Virus-like_particle https://en.wikipedia.org/wiki/Virus-like_particle https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905985/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905985/ (Disclosure: I was a participant in the phase 3 trial of Medicago's CoVLP/Covifenz vaccine)
lamontcg 4y ago
Nanoparticles are what the mRNA SARS-CoV-2 vaccine are packaged in. They're lipid particles that are chemically very similar to your cell walls so they just fuse with the wall and then release their payload inside the cell. That doesn't have anything to do with the target though. The stalk of the virus is difficult to target and not really possible with the existing way that influenza vaccines are manufactured with an inactivated virus process. So you wind up with the whole proteins and no good way to target segments. By using mRNA technology you can specify which protein you want to target or which segment of protein you want to target. It can also be useful to make edits to the protein sequence like the prefusion stabilization in the mRNA vaccines. When you get the inactivated influenza vaccine you're still getting HA stalks attached to the HA protein and for whatever reason the immune system doesn't target the stalk sections well. So the idea is that you hit the immune system with a payload of only HA stalks and then hopefully the immune system pumps out antibodies specific for that which will then be resistant to genetic drift.

Can anyone speak to these nanoparticles and why this technique hasn't been seen before? Maybe more generally why we haven't targeted this part of the virus that doesnt change?

Moto7451 4y ago

This is all state of the art research. It’s the same reason we didn’t have mRNA vaccines 10 years ago.

BitwiseFool 4y ago
And from what I understand, mRNA vaccine technology was languishing before the urgency of Covid put their development into overdrive.
- origin_path 4y ago
  It wasn't languishing, that word implies people knew about it but weren't paying attention or trying to make it work. mRNA based drugs hadn't launched because repeat dosings created serious side effects, as the body seemed to start reacting to the lipid capsule. From an article in 2017: https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ "for its chemists, those [lipid] nanoparticles created a daunting challenge: Dose too little, and you don’t get enough enzyme to affect the disease; dose too much, and the drug is too toxic for patients." "the Crigler-Najjar treatment has been indefinitely delayed, an Alexion spokeswoman told STAT. It never proved safe enough to test in humans, according to several former Moderna employees and collaborators who worked closely on the project. Unable to press forward with that technology, Moderna has had to focus instead on developing a handful of vaccines" Note the following paragraphs: "mRNA is a tricky technology. Several major pharmaceutical companies have tried and abandoned the idea, struggling to get mRNA into cells without triggering nasty side effects [snip] The indefinite delay on the Crigler-Najjar project signals persistent and troubling safety concerns for any mRNA treatment that needs to be delivered in multiple doses, covering almost everything that isn’t a vaccine" In 2017 mRNA was considered "tricky" and with "nasty side effects". It was considered safe for vaccines by Moderna only because, they claimed, vaccines don't require repeat doses. This is surprising given that some countries now want to make mRNA vaccination a regular yearly event. The reason they didn't focus on vaccines originally is related to that belief - vaccines are traditionally something you take once and are then protected for decades or for life. They are cheap and often bought by governments that demand bulk discounts, thus they are poor business compared to drugs that may require you to take them every week.
  - hahaitsfunny 4y ago

sterlind 4y ago

We didn't know what part of the virus would change before the virus started changing. A small number of patients developed broadly-neutralizing antibodies (bnABs), which not only wiped out Covid classic, but kept working well against the other variants too. Once we found out what part of the spike protein those antibodies bound to, then we knew what to target. But it's still not easy to raise antibodies to recognize specific sites on a protein - the more "context" you include, the more likely it is that your immune system will find another, less effective, handle on the protein to grab and call it a day. I suppose we knew about pan-coronavirus conserved sites before, but it (imo) would have been too risky to try targeting those sites with the first mRNA vaccines - one experimental technology at a time.

ch4s3 4y ago
If targeting pan-coronavirus conserved sites works out, it will be big news for other vaccines in the future.

sp332 4y ago

Each nanoparticle holds 20 antigens next to each other. The researchers say this provides a stronger signal to the immune system that there is a danger. https://www.niaid.nih.gov/news-events/nanoparticle-flu-vaccine https://www.niaid.nih.gov/news-events/nanoparticle-flu-vacci...

mikepurvis 4y ago

Without really knowing the first thing about it, I'm curious if the nanoparticles discussed here are the same or similar to the "virus-like particles" that Medicago describes as being the key to their vaccine technology: https://medicago.com/en/our-technologies/virus-like-particles/ https://medicago.com/en/our-technologies/virus-like-particle... https://en.wikipedia.org/wiki/Virus-like_particle https://en.wikipedia.org/wiki/Virus-like_particle https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905985/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905985/ (Disclosure: I was a participant in the phase 3 trial of Medicago's CoVLP/Covifenz vaccine)

lamontcg 4y ago

Nanoparticles are what the mRNA SARS-CoV-2 vaccine are packaged in. They're lipid particles that are chemically very similar to your cell walls so they just fuse with the wall and then release their payload inside the cell. That doesn't have anything to do with the target though. The stalk of the virus is difficult to target and not really possible with the existing way that influenza vaccines are manufactured with an inactivated virus process. So you wind up with the whole proteins and no good way to target segments. By using mRNA technology you can specify which protein you want to target or which segment of protein you want to target. It can also be useful to make edits to the protein sequence like the prefusion stabilization in the mRNA vaccines. When you get the inactivated influenza vaccine you're still getting HA stalks attached to the HA protein and for whatever reason the immune system doesn't target the stalk sections well. So the idea is that you hit the immune system with a payload of only HA stalks and then hopefully the immune system pumps out antibodies specific for that which will then be resistant to genetic drift.