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COVID-19 vaccine discussion


Texas Jeff

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3 hours ago, midtown said:

Dear god.  I am in the hospital and about to die from covid.  Why didn't you save me?   Hey dumbass. I sent you vaccines.

Now that you mention it . Update on my cousin who was full on trump and anti vax. Been in a hospital for a couple weeks now. 

She had been doing better and they tried to wake her today and that didn't go well. She is sedated again. Nothing but payers and the lord will get her through this. This is fucking ridiculous. Take the vaccine 

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Now that you mention it . Update on my cousin who was full on trump and anti vax. Been in a hospital for a couple weeks now. 
She had been doing better and they tried to wake her today and that didn't go well. She is sedated again. Nothing but payers and the lord will get her through this. This is fucking ridiculous. Take the vaccine 
I hope she pulls through. I actually don't blame the victims. This is a cult of misinformation and people are dying for their false prophet who btw took the freaking vaccine
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1 hour ago, midtown said:
1 hour ago, Zepol87 said:
Now that you mention it . Update on my cousin who was full on trump and anti vax. Been in a hospital for a couple weeks now. 
She had been doing better and they tried to wake her today and that didn't go well. She is sedated again. Nothing but payers and the lord will get her through this. This is fucking ridiculous. Take the vaccine 

I hope she pulls through. I actually don't blame the victims. This is a cult of misinformation and people are dying for their false prophet who btw took the freaking vaccine

I blame them. If that same jackass told them stop signs and red lights were the work of commie liberals trying to deny them their freedoms, would they listen?

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Continuing our Surly literature review, I ran across a couple interesing things today.  The first is more booster data relating to younger age groups than what was published in the NEJM paper I posted yesterday.  

Israeli_Data.thumb.png.0f2e430a40799f5bb3bddf92f9edd224.png

This reinforces the data we have seen that in younger healthy populations the breakthrough cases are increasing but remain mild in nature.

Also, this encouraging preprint out of the UK was posted today.

This is of course very preliminary, but I liked the concluding statement: 

Quote

Although there is considerable uncertainty attached to any extrapolation into the future, the best estimate we can make on the basis of the data available is that the rapid waning of efficacy against COVID-19 in the first two months after the second dose tapers off thereafter and that the trajectory is consistent with a long-term efficacy of about 80% against hospitalisation. Thus at present there is no clear evidence to support a policy of delivering booster doses to the entire population, rather than to vulnerable individuals for focused protection.

  Given the slow mutating nature of coronaviruses I'm optimistic in the long term efficacy of our vaccines. 

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10 hours ago, Dontshootrude said:

Given the slow mutating nature of coronaviruses I'm optimistic in the long term efficacy of our vaccines. 

I'm not so sure. That article that you linked a few days ago seemed to miss some important points. While mutations from within vaccinated individuals may be lower than in unvaccinated individuals, a mix of unvaccinated individuals and vaccinated individuals will potentially lead to new strains that are more infectious and perhaps even circumvent the spike protein antibodies. I think using the spike protein only in an mRNA vaccine will prove to be a mistake and more targets should be included in the vaccine. In other words, related to the quoted part of your post, I am not confident in the long-term efficacy of the current vaccines on the market. I don't even think you are that confident as you think the lipid encapsulation of the mRNA may cause a decrease in efficacy as more boosters are given. I think this is possible as well.

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1 hour ago, Bevo said:

I'm not so sure. That article that you linked a few days ago seemed to miss some important points. While mutations from within vaccinated individuals may be lower than in unvaccinated individuals, a mix of unvaccinated individuals and vaccinated individuals will potentially lead to new strains that are more infectious and perhaps even circumvent the spike protein antibodies. I think using the spike protein only in an mRNA vaccine will prove to be a mistake and more targets should be included in the vaccine. In other words, related to the quoted part of your post, I am not confident in the long-term efficacy of the current vaccines on the market. I don't even think you are that confident as you think the lipid encapsulation of the mRNA may cause a decrease in efficacy as more boosters are given. I think this is possible as well.

I disagree.  Truth is there are fundamental biological reasons why I think it unlikely that COVID will be able to find a mutation that will significantly escape our vaccines.  When replicating, coronaviruses, including COVID, have a proofreading mechanism (PDF warning) that will verify the genetic sequence that is being replicated. It is not as robust as that in eukaryotic cells (human, mammals for example) whence the mutations we do see, but it does exist.  Compare COVID to a true rapidly mutating virus like flu.  Flu has two mechanisms that allow it to radically mutate in short periods of time.

1. Genetic drift - random point mutations in the genome from the highly error prone replication enzymes that lack proof reading that it uses to replicate its RNA genome

2. Genetic shift - completely swapping out entire gene segments for new ones creating a whole new unique flu virus. Only Influenza A viruses can do this which is why they are responsible for the pandemic strains.

To highlight this, check out the two files attached to this post.  The COVID_Variant_Alignment file are the top five variants of concern aligned against the original COVID sequence provided to CDC back in January 2020 that the vaccine was designed against. An * under the specific base means the nucleotide is the same among all six strains. Notice how much of the sequence is the same among all six, and you really must hunt to find changes. I've also attached an alignment from a surface protein of flu, a true rapidly mutating virus for comparison. Notice how inconsistent the flu is and you'll see why it is so challenging to design effective vaccines and therapeutics.

Shifting back to the vaccines, the spike protein is a big protein.  I've seen studies that report CD8+ (T killer cells, the ones that seek out and kill infected cells) recognizes 52 epitopes (spots on the protein).  CD4+ cells (T helper cells, which help drive antibody responses) recognize 23 epitopes across the entire spike protein.  I'll try to find my references for this later, but offhand I can't recall exactly which study addressed this.  It is hard to imagine, given how stable COVID is, that it will find a way to alter all of these regions and still remain infectious.

Comparing the Beta variant vs Delta is encouraging too.  Beta is actually more genetically distant than delta and the vaccine was less effective against it compared to delta.  But Delta has outcompeted it nonetheless.  

This is a good article that partially addresses what I'm saying above.

And one finally thing I should mention regarding the immune response to the lipid capsule delivery vehicle.  I wouldn't  say I'm extremely worried about this. I'd just like to see it addressed before I take a shot that decreases my risk of hospitalization from 1 in 300,000 to 1 in a couple of million.   

COVID_Variant_Alignment.txt Influenza_H1gene_alignment.txt

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54 minutes ago, Dontshootrude said:

I disagree.  Truth is there are fundamental biological reasons why I think it unlikely that COVID will be able to find a mutation that will significantly escape our vaccines.  When replicating, coronaviruses, including COVID, have a proofreading mechanism (PDF warning) that will verify the genetic sequence that is being replicated. It is not as robust as that in eukaryotic cells (human, mammals for example) whence the mutations we do see, but it does exist.  Compare COVID to a true rapidly mutating virus like flu.  Flu has two mechanisms that allow it to radically mutate in short periods of time.

1. Genetic drift - random point mutations in the genome from the highly error prone replication enzymes that lack proof reading that it uses to replicate its RNA genome

2. Genetic shift - completely swapping out entire gene segments for new ones creating a whole new unique flu virus. Only Influenza A viruses can do this which is why they are responsible for the pandemic strains.

To highlight this, check out the two files attached to this post.  The COVID_Variant_Alignment file are the top five variants of concern aligned against the original COVID sequence provided to CDC back in January 2020 that the vaccine was designed against. An * under the specific base means the nucleotide is the same among all six strains. Notice how much of the sequence is the same among all six, and you really must hunt to find changes. I've also attached an alignment from a surface protein of flu, a true rapidly mutating virus for comparison. Notice how inconsistent the flu is and you'll see why it is so challenging to design effective vaccines and therapeutics.

Shifting back to the vaccines, the spike protein is a big protein.  I've seen studies that report CD8+ (T killer cells, the ones that seek out and kill infected cells) recognizes 52 epitopes (spots on the protein).  CD4+ cells (T helper cells, which help drive antibody responses) recognize 23 epitopes across the entire spike protein.  I'll try to find my references for this later, but offhand I can't recall exactly which study addressed this.  It is hard to imagine, given how stable COVID is, that it will find a way to alter all of these regions and still remain infectious.

Comparing the Beta variant vs Delta is encouraging too.  Beta is actually more genetically distant than delta and the vaccine was less effective against it compared to delta.  But Delta has outcompeted it nonetheless.  

This is a good article that partially addresses what I'm saying above.

And one finally thing I should mention regarding the immune response to the lipid capsule delivery vehicle.  I wouldn't  say I'm extremely worried about this. I'd just like to see it addressed before I take a shot that decreases my risk of hospitalization from 1 in 300,000 to 1 in a couple of million.   

COVID_Variant_Alignment.txt 289.71 kB · 0 downloads Influenza_H1gene_alignment.txt 117.16 kB · 0 downloads

Yeah, I already know this technically, but life finds a way. I agree that you aren't going to find an event that circumvents all 52 epitopes - that just doesn't happen in the short run unless the virus picks up pieces of nucleic acids from other viruses. But, over time, you will see single shift mutations that become predominant followed by other mutations and others that will eventually lead to "better" strains. Concurrently, I think we will see an increasing number of adverse events with the vaccines if we are getting boosters every 8mo. for a lifetime. Those adverse events may be anaphylaxis, pericarditis, endocarditis, or simply decreased uptake of the vaccine. So, we can agree to disagree, but turning the disease into an annual non-event will be a problem and eradication through a more effective vaccine is a much, much better outcome.

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58 minutes ago, Satoshi said:

The second slide tells me there’s no indication for widespread boosters in the population under 75. Over could be a debate but still pretty strong coverage. 

I think that we will see a limited booster roll out. The way the FDA framed the topical question for the meeting, however, asks them to address whether a booster is warranted in individulas 16 and older, so will be interesting to see where they actually land with a decision on the question posed by FDA. 

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1 hour ago, Dontshootrude said:

I disagree.  Truth is there are fundamental biological reasons why I think it unlikely that COVID will be able to find a mutation that will significantly escape our vaccines.  When replicating, coronaviruses, including COVID, have a proofreading mechanism (PDF warning) that will verify the genetic sequence that is being replicated. It is not as robust as that in eukaryotic cells (human, mammals for example) whence the mutations we do see, but it does exist.  Compare COVID to a true rapidly mutating virus like flu.  Flu has two mechanisms that allow it to radically mutate in short periods of time.

1. Genetic drift - random point mutations in the genome from the highly error prone replication enzymes that lack proof reading that it uses to replicate its RNA genome

2. Genetic shift - completely swapping out entire gene segments for new ones creating a whole new unique flu virus. Only Influenza A viruses can do this which is why they are responsible for the pandemic strains.

To highlight this, check out the two files attached to this post.  The COVID_Variant_Alignment file are the top five variants of concern aligned against the original COVID sequence provided to CDC back in January 2020 that the vaccine was designed against. An * under the specific base means the nucleotide is the same among all six strains. Notice how much of the sequence is the same among all six, and you really must hunt to find changes. I've also attached an alignment from a surface protein of flu, a true rapidly mutating virus for comparison. Notice how inconsistent the flu is and you'll see why it is so challenging to design effective vaccines and therapeutics.

Shifting back to the vaccines, the spike protein is a big protein.  I've seen studies that report CD8+ (T killer cells, the ones that seek out and kill infected cells) recognizes 52 epitopes (spots on the protein).  CD4+ cells (T helper cells, which help drive antibody responses) recognize 23 epitopes across the entire spike protein.  I'll try to find my references for this later, but offhand I can't recall exactly which study addressed this.  It is hard to imagine, given how stable COVID is, that it will find a way to alter all of these regions and still remain infectious.

Comparing the Beta variant vs Delta is encouraging too.  Beta is actually more genetically distant than delta and the vaccine was less effective against it compared to delta.  But Delta has outcompeted it nonetheless.  

This is a good article that partially addresses what I'm saying above.

And one finally thing I should mention regarding the immune response to the lipid capsule delivery vehicle.  I wouldn't  say I'm extremely worried about this. I'd just like to see it addressed before I take a shot that decreases my risk of hospitalization from 1 in 300,000 to 1 in a couple of million.   

COVID_Variant_Alignment.txt 289.71 kB · 0 downloads Influenza_H1gene_alignment.txt 117.16 kB · 0 downloads

Also some articles that may be of interest:

 

Ab response to SARS-CoV-2

https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1.full

 

SARS-CoV-2 viral targets

https://www.nature.com/articles/s41577-020-00480-0

 

Just a review article on lipid encapsulation of mRNA (You would be one of the few who may be interested). A long-time ago I worked on transfection agents which is where all this derived. BTW, there is a guy in Austin who was a director for the Bay Area company that developed the lipid encapsulated Amphotericin B and daunorubicin products.

https://www.nature.com/articles/s41578-021-00358-0

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439223/

Edited by Bevo
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10 minutes ago, Satoshi said:

 

 

What The Hell Just Happened Reaction GIF

I've always had a part of me that was drawn to a hermit lifestyle, and I'll be damned if the stupidity on full display the last year and half doesn't have me shopping for available remote mountaintops.  I don't know what the wife and kids will think about it, but living amongst humans is getting to be too much.

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2 hours ago, Bevo said:

Also some articles that may be of interest:

 

Ab response to SARS-CoV-2

https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1.full

 

SARS-CoV-2 viral targets

https://www.nature.com/articles/s41577-020-00480-0

 

Just a review article on lipid encapsulation of mRNA (You would be one of the few who may be interested). A long-time ago I worked on transfection agents which is where all this derived. BTW, there is a guy in Austin who was a director for the Bay Area company that developed the lipid encapsulated Amphotericin B and daunorubicin products.

https://www.nature.com/articles/s41578-021-00358-0

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439223/

That nature review on lipid delivery of mRNA was interesting  It lead me to this paper in which people got eight shots and they were continuing to develop good immune responses.  That is encouraging news and helps alleviate my concerns regarding decreasing efficacy due to the immune system recognizing the capsule!  

As to the other papers, those were published right as we were mass deploying the vaccines.  I was more concerned then, but thankfully recent data has held up well, especially against severe disease.  I'm optimistic that will continue.

ETA: I also found the references that highlight the diverse array of vaccine induced epitopes and how well they are holding up for the vaccines.

https://www.biorxiv.org/content/10.1101/2021.02.27.433180v1

https://www.sciencedirect.com/science/article/pii/S2666379121002044

Edited by Dontshootrude
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41 minutes ago, Satoshi said:

 

Funny/CSB story.  CDC has protesters come and go, but there is one dude that is always right outside CDC rain or shine, hot or cold, with about 10 signs walking up and down the sidewalk that say things like "Infertility," "Genocide," "Obey," etc.  As crazy as he is I tip my cap to him for being so incredibly dedicated and so confident in himself that he can do that just about every day by himself. It is a shame he has latched onto something this crazy, because if he would have picked something productive no doubt he would have been highly successful. 

Something tells me the Nicki Minaj protesters won't be so driven.  

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19 minutes ago, Dontshootrude said:

Funny/CSB story.  CDC has protesters come and go, but there is one dude that is always right outside CDC rain or shine, hot or cold, with about 10 signs walking up and down the sidewalk that say things like "Infertility," "Genocide," "Obey," etc.  As crazy as he is I tip my cap to him for being so incredibly dedicated and so confident in himself that he can do that just about every day by himself. It is a shame he has latched onto something this crazy, because if he would have picked something productive no doubt he would have been highly successful. 

Something tells me the Nicki Minaj protesters won't be so driven.  

There was a guy who protested every day outside of the Planned Parenthood that is caddy corner to the closest liquor store from my house.  3 or 4 months ago he went away and haven’t seen him since.  Guessing either Covid got his ass or that Planned Parenthood closed and building management just hasn’t removed the signage yet.

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Interesting MMWR published today.

https://www.cdc.gov/mmwr/volumes/70/wr/mm7038e1.htm?s_cid=mm7038e1_w

Key table:

E_gQtvjUYAIVYgC.thumb.jpg.0a6d87b5de8e5e6185c3712cbb2dbf8f.jpg

 

Moderna dominance continues.

This is in 21 hospitals.  It is good news, but Jesus, the UK and Israel are making the US public health system look horrible.  Our data sets are small, inconsistent, and fragmented.  It is really difficult to get good large scale data sets in the US in a timely fashion.  The pandemic has really exposed how vulnerable and unorganized we are.

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200.gif
I've always had a part of me that was drawn to a hermit lifestyle, and I'll be damned if the stupidity on full display the last year and half doesn't have me shopping for available remote mountaintops.  I don't know what the wife and kids will think about it, but living amongst humans is getting to be too much.

I think people place too much emphasis on their careers. I wish we could all live in the mountains at high altitude. That’s where I see myself in five years.
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3 minutes ago, Gatorubet said:


So - you want us all to die of wildfire?

Well, if no one lived in Central Cali. and LA, there would be less smoke blocking the views in the Sierras and Rocky's. Plus, when Coastal California falls into the ocean, the Sierras, Mojave Desert, and Death Valley will become prime property. 

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