Michelle Price

frontiersin.org/journals/imm… 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).

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: sanofiflushots.com/flu-shot-…

🚨💉Big vaccine news today: AHIP, which is the national trade association representing the health insurance industry, announced that health insurers will continue to cover all ACIP-recommended immunizations as of September 1 - including the updated COVID-19 vaccines - through the end of 2026. This essentially makes this week's ACIP meeting a moot point, and ensures that Novavax will be available for free to anyone with a health insurance plan once it becomes available in the coming weeks regardless of what ACIP decides to recommend. Once again, there is absolutely no reason to rush out and get mRNA. AHIP statement: ahip.org/news/press-releases… AHIP members: ahip.org/members