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IMPORTANT ANNOUNCEMENT FOR AUSTRALIANS SEEKING NUVAXOVID (NOVAVAX).
Today I received a Nuvaxovid (Novavax) vaccination - my first COVID-19 vaccination in more than three years.
https://t.co/PuFvE1YCKg
This new paper on the mRNA vaccines really helps to explain some of the benefits of Novavax. The main focus is on mRNA’s cardiovascular side effects (which is a separate issue), but what’s most interesting to me is that is helps explain why we get less protection against infection across variants with mRNA when compared to Novavax.
Those benefits are at least somewhat related to Novavax’s focus on CD4+ T cells and the S2 subunit of the SARS2 spike protein, which we did already know, but now we understand a key mechanism for WHY Novavax is so much better at it than the mRNA vaccines.
To start, a couple brief summaries/reminders:
1. How the SARS2 spike protein works: The spike is made up of 3 main parts - The NTD (N-terminal domain) and RBD (receptor binding domain) in the S1 subunit, and the S2 subunit. The vast majority of mutations happen on S1, while S2 is a lot more stable. Since S1 contains the RBD, which is where the virus attaches to our ACE2 receptors, it does tend to be more important to have the immune system mount a response to S1 epitopes for the purpose of preventing infection. However, S2 is still extremely important when trying to generate an immune response across multiple variants - since, like I mentioned before, S2 is a lot more stable.
2. How T cells work: CD8+ cytotoxic T cells are the cells that directly kill cells that are infected by a virus like SARS2. CD4+ Helper T cells are the cells that coordinate the entire immune response: they identify pathogens and signal to other immune cells (B cells, macrophages, and the aforementioned CD8+ T cells, etc.) to destroy pathogens.
Now, here’s what we learned and had confirmed in this new paper: Essentially, the mRNA vaccines can only induce a robust CD4+ response against the S1 subunit, and NOT against the S2 subunit.
Why?
The paper found that, after our body produces the spike protein post-mRNA vax, it gets broken back down into its two main parts - S1 and S2 - while still inside of our cells. After that breakdown occurs, only the S1 subunit was detected outside of the cells that were tested, while the S2 subunit remained inside of all of the cells tested.
Next, there are two main pathways that generate immunity: MHC Class I (intracellular) - which activates CD8+ cells, and MHC Class II (extracellular) - which activates CD4+ cells.
So, essentially, since S2 is not present extracellularly, the mRNA vaccines are not generating CD4+ cells (which are required for coordinating the entire immune response) primed against the S2 subunit (which is the key to maintaining a response across a wider range of variants).
Fake immigration “hotline” gets a call from a teacher asking to deport a kindergarten student’s parents, saying “we normally don’t have Hispanics here” and they “don’t belong.” The host mocks her, saying “yeah, the little fellow could be a national security threat.”
“It’s the Omicron era. Covid is over. Nothing to worry about regarding effects on the brain.
It’s mild now.”
Whatever you want to tell yourself.
I’ll tell you how it is.
Acetylsalicylic acid disrupts SARS-CoV-2 spike protein glycosylation and selectively impairs binding to ACE2
‼️YOUR ATTENTION: Very interesting Italian work, supporting earlier science findings: ASPIRIN!
➡️Acetylsalicylic acid (ASA/aspirin) has shown potential in reducing COVID-19 severity via anti-inflammatory effects, but its direct impact on SARS-CoV-2 spike S1 protein binding to ACE2 receptor was unknown.
➡️ASA directly interferes with S1-ACE2 binding, potentially mitigating viral entry and tissue injury.
➡️In Vitro:
- ASA pre-incubation dose-dependently reduced recombinant S1 binding to ACE2 on Vero cells and in ELISA assays
-Limited cytopathic effects of live SARS-CoV-2 (specific to ASA, not paracetamol).
➡️In Vivo:
- In human ACE2 transgenic mice, ASA-treated S1 caused markedly less lung injury, fibrosis (reduced fibronectin/collagen), and inflammation (fewer macrophages/neutrophils) than untreated S1.
➡️Mechanism:
- Glycoproteomics revealed ASA alters S1 glycosylation, notably reducing N-glycosylation at N61 and O-glycosylation at S325, with increased acetylation.
➡️Experimental confirmation:
- Site-directed mutagenesis creating the N61D/S325A double mutant in the spike protein reduced ACE2 binding in vitro and lung pathogenicity in vivo, thereby replicating the protective effects of ASA.
➡️Conclusions:
- ASA exhibits a novel antiviral action by disrupting spike glycosylation, supporting its repurposing as a low-cost intervention to prevent COVID-19 progression and related complications.
➡️No clinical doses are discussed, only a 20mg/L in an In-vivo mouse model. 🤔
➡️‼️"These findings unveil a previously unrecognized antiviral activity of ASA, providing a molecular rationale for its repurposing as a low-cost, readily available intervention to prevent the progression from mild to severe COVID-19."
So, Aspirin directly impairs SARS-CoV-2 spike protein binding to ACE2 by disrupting its glycosylation, thereby reducing viral entry, cytopathic effects, and lung injury in preclinical models.
https://t.co/BrPgYHxWmc
I never thought I’d be writing this.
After years of advocating for clean air and protecting kids during an ONGOING PANDEMIC, my daughter’s high school is trying to ban masks.
My kid is a freshman.
Illinois Section 2A tennis champion and state qualifier.
Healthy. Driven. Focused.
All As.
And her school wants to take away her right to protect herself from a virus known to cause brain damage, vascular injury, immune dysfunction, and Long Covid.
Let that sink in.
On January 26, @Unit4Schools plans to enforce a #MaskBan.
This is not about politics.
This is about bodily autonomy.
This is about disability discrimination.
This is about children’s rights.
If you think this ends quietly, you are mistaken.
@ACLU@Liesl4CleanAir@luckytran
📄 Receipts + documentation:
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Share this. Screenshot it. Tag people.
Because kids deserve clean air in school.
https://t.co/OfS8GDIFKN
Some good news from Sanofi: They are telling us that a locator tool for Novavax will be going live late next week.
So, if things work out like they’re supposed to, @Friesein and I might only have about 10 more days of hard work to do, and the rest of y’all might only have about 10 more days of having to scour Twitter threads to locate doses.
Sanofi definitely should have the capability to produce a functional and useful tool. This is their wheelhouse, and they host a very functional locator for their flu shots as well: https://t.co/r1OdMg76g6