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TZ's avatar

I'm not sure I get this--he suggests the spike protein is inherently more unstable than other proteins in the virus. That is based on observation over time. But that's not obvious to me. An alternative hypothesis is the spike protein is no more unstable than any other protein but we have imposed immense selection pressure on the spike protein, which has accelerated its evolution relative to the other elements of the virus. Keep in mind that during the entire first year of the pandemic we only had one variant, from the original Wuhan to the alpha, which was modest. Since vaccination, however, we have had waves of variants.

So my concern is that if we "chose" more stable proteins to target with vaccines, that would simply make those proteins more unstable.

Apparently targeting some proteins, especially less active proteins such as the Nucleocapsid, also raises elevated concerns about ADE that narrowly targeting the spike does not. This is very murky though and I've tried to find more discussion on this point, but it doesn't seem to be widely discussed so that might not be accurate. All I can find really is this: https://www.science.org/content/blog-post/antibody-dependent-enhancement-and-coronavirus-vaccines

There is a confusing update in the key passage there that suggests the "correction" is not to say the Nucleocapsid does not risk ADE but that the spike has a lower risk of ADE:

"The SARS experience taught us a lot of extremely useful lessons, as it turned out. SARS-Cov-2 is rather closely related to the 2003 SARS coronavirus, and if you're going to have a worldwide pandemic, you're far better off with one that's so much like something you've already poured R&D investments into! In this case, the two big take-homes were that coronavirus vaccines could indeed suffer from ADE, and that this seemed to depend on which protein you chose to base your vaccine around. Specifically, it was the vaccines that targeted the N (nucleoprotein) antigen of the coronavirus that had ADE problems, while the ones that targeted the S (Spike) protein did not. Update: this isn't accurate. There was trouble after immunization with a nucleoprotein-directed vaccine, but ADE could also be seen with some of the Spike-directed vaccine candidates as well - see reviews here, here, and here. That experience was thoroughly taken to heart in the vaccine developments of the last year: no one, to the best of my knowledge, even bothered to target the SARS-Cov-2 N protein at all, for just this reason."

That's a long quote, so to highlight the key sentence, "That experience was thoroughly taken to heart in the vaccine developments of the last year: no one, to the best of my knowledge, even bothered to target the SARS-Cov-2 N protein at all, for just this reason."

Yet I am now hearing a wide range of people arguing that we should target a broader array of proteins or asking why the vaccines don't target the Nucleocapsid. If this is correct, it is because targeting those proteins increase the risk of ADE significantly (which is already non-zero with the spike).

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DanBC's avatar

Consider this. Trusting ANY article published in the establishment press, is likely a mistake, and, disinformation from TPTB.

The censorship and shunning, of all things countr to the official narrative is pervasive and widespread across society.

When one can’t trust our health agencies, our medical boards, our media and our governments, becauseTHEY ALL ALIGN WITH THE OFFICIAL NARRATIVE, then we must question everything and, NEVER assume anything we read or hear is factual or believable.

Those are the times we now live in.

Just look at the US and Canadian Governments, all their toadies and their public miscreants. There’s not a word they say, that is trustworthy. The disease is from the top, down.

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Wild Bill's avatar

"Build back better" means getting rid of all of these agencies and corruption, and creating a smaller and kinder government like, let's say, what we had ca. 1790. Respecting the limited powers of the Constitution. There were 3 cabinet level agencies in the 'old days' - Army (then War and now Defense), State and Treasury. And they were all much less powerful and influential than today.

Well, we can hope anyway.

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Tom Hogan's avatar

No, we have all been exposed to covid by now and the natural immune response has exerted selection pressure. The unvaccinated have the best response to covid now, barring vitamin D deficiency or some other way that immune systems are compromised.

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lymond's avatar

And yet, one of the original studies on covid showed cross-reactive immunity with the N protein from the original SARS.

https://www.nature.com/articles/s41586-020-2550-z

"Seven out of eight individuals tested showed clear, robust expansion of N-reactive cells (Fig. 3e) and ICS confirmed that individuals who recovered from SARS had SARS-CoV N-reactive CD4 and CD8 memory T cells."

Capricor had an interesting vaccine candidate that used an exosome delivery system and displayed both the spike and nucleocapsid protein, but I guess they didn't pay off the right people in the FDA.

https://www.fiercepharma.com/drug-delivery/capricor-touts-exosomes-as-better-mrna-delivery-vehicle

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Making waves's avatar

Pasting a portion of my comment from above regarding ADE and coronaviruses:

Going off of memory here, gonna have to dig through my old notes. While it's true that some studies showed that S-only vaccines might be less at risk of ADE/VED, there were also studies that showed the combo of S- and N- might be superior (gotta double check) or that certain adjuvants might be problematic. After looking into this question, I came to the conclusion that at that time the results to date were conflicting, but they had to test something...

Most concerning to me were two different things, however. #1) I was deeply disturbed that previous studies on average only challenged the test animal a few weeks after finishing the vaccine series. Given that a leading theory for ADE proposes that waning immunity against the pathogen is a key cause, how does making claims about ADE, when test animal immunity is at peak, make any sense at all?

Answer: it doesn't. Maybe they didn't want to report negative outcomes, so they looked when they knew it wasn't likely to be present, thereby fixing their results to show the research in more favorable light. It's also more costly to extend studies and maybe lifespan of animals comes into play, but I can't help but smell publication bias. Whatever the reason, the study construct seems inadequate to best answer that question.

#2) Animals that are used to test coronavirus vaccines and ADE are not able to replicate the severe pathology that occurs in humans. If the test animal doesn't show severe symptoms (with the associated pathology?), how can you get meaningful answers about such a topic? Surrogate markers would likely only get you so far. Again, seems rather inadequate, even if they have no other option.

To me, their knowledge regarding coronavirus vaccines and ADE was half-baked at best. One of the many reasons it seemed the opposite of cautious to disseminate them so widely, so fast.

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