#Moderna MRNA

[phillyyardyvibes]

https://rumble.com/v5zsg1z-nasdaq-100-rebalanced-microstrategy-palantir-and-axon-in-milestone-hits-20k.html

Nasdaq 100 Rebalanced: MicroStrategy, Palantir & Axon In, Milestone Hits 20K! The Nasdaq 100 has undergone its latest rebalancing, welcoming MicroStrategy, Palantir, and Axon to the prestigious index

[dosesofcommonsense]

Creating new problems needing new solutions. Have they ever cured anything? No. Why would they do that? They’d lose patients.

[pandemic-info]

AMAZING, informative thread by Michael Lin, MD PhD (Assoc. Professor of Neurobiology & Bioengineering @Stanford | https://linlab.stanford.edu/) about the differences between Novavax & mRNA.

& Full thread pasted below:

(P.S. I apologize about the images, Tumblr is not letting me add ALT text for some reason. The original on ThreadReader might be better in that case.)

Flew in from Asia today to learn the exciting news that Novavax's JN.1 booster has been approved! So happy that the delay relative to RNA vaccines is less than a week. People will finally have a choice of RNA vs protein vaccines this fall. What are the differences?

I made this graphic to show how different vaccine types work (back in 2021). We can just look at line 1 (protein vax like Novavax) and line 3 (RNA vax). In protein vax, antigen-presenting cells take up the antigen to activate B cells and Thelper cells....

In RNA vax, your muscles cells take up RNA and translate it into antigen. This process tends to be a bit inflammatory (apparently that's inherent to RNA uptake) so some cells die and release proteins that are also taken up by antigen-presenting cells. The main differences between protein and RNA vax in practice are threefold: 1.  Cellular immunity, meaning CD8 cytotoxic T cell responses: RNA vax elicit this, whereas Novavax CTL responses are minimal.

RNA vax probably do so because having foreign antigens in muscle cells looks like a virus has infected those cells. The antigens are presented on MHC-I (whereas proteins ingested by antigen-presenting cells are expressed on MHC-II), and this is necessary for activating CD8 CTLs. 

Cellular immunity provides a backup and mopping-up function after antibodies have cleared away viruses (note I did not use the term neutralize; more on why later), and lack of cellular immunity may cause prolonged disease. But cellular immunity is long-lived and broad-spectrum... 

If you've had a RNA vax or a SARSCoV2 infection within the last 3 years, then you have cellular immunity. It's broad-spectrum as CTLs recognize many conserved regions of the spike (if you've only been vaccinated and never infected) or other viral proteins if you were infected.

And if you've never had a CTL response (because you only took Novavax vaccines and were never infected — a vanishingly small possibility), then if you get infected you will develop a CTL response in week 1 while antibodies are clearing the virus, after which CTLs help "mop up"

As you can see, I don't think much about keeping CTLs up. Once you have a CTL response (from RNA vax or infection), it stays with you. If you don't have one, you'll develop it during illness. It doesn't help prevent infection and having it ahead of time makes little difference.  

The second difference between protein vax and RNA vax is the peak amplitude of antibodies. Peak antibody levels are higher with RNA vax. This is certainly an advantage of RNA, but it only lasts for 2-6 weeks after inoculation. Titers drop dramatically after that.

This wave is going strong, and does not look like it will peak within 6 weeks. There's a lot of disease going on now, as there was a month ago. It seems likely there will be virus going around at Halloween and Thanksgiving gatherings, and Christmastime-New Year parties too.  

Data on superiority of RNA-boosted Abs in month 1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576915/ As waves tend to last 3 months (and this one appears might even become 6 months), a 6-week period of somewhat higher protection doesn't seem so useful as how well a vax works over the entire wave, IMO.

And the data do show that in the long-term (measured from 3mo post-vax) Novavax is as good as RNA. Here's one study: https://www.sciencedirect.com/science/article/pii/S0092867422006535

Now if there were no price to pay for having one month of high antibodies, then sure, why not RNA. But that brings us to difference #3 between protein and RNA vaccines: the RNA vax are stronger in their adverse effects on the immune system than any other vaccine we've ever taken.

IgG is the major class of antibodies your B cells make. When they encounter the same antigen repeatedly, often seen in autoimmunity or with parasitic infections, the IgG genes undergo "isotype switching" to IgG4, which lacks any of the "Fc effector" functions of other IgG types. The Fc functions include antibody-mediated recruitment of phagocytic cells to engulf and destroy antibody-coated viral particles. We hear a lot about neutralizing antibodies because it's easy to test how well your blood neutralizes SARSCoV2 from entering cells, but in the body… 

It's more efficient for an antibody to tag a virion, get the virion engulfed and destroyed, and for the antibody to be recycled to repeat the process. If neutralization were the only thing, we'd need more antibody molecules than spike proteins across all virions, a tall order.

An issue that's now well known is that RNA vaccines cause isotype switching to IgG4, which lacks these Fc functions. This was not the case with earlier vaccines, so appears to be the result of the strong B cell stimulation performed by RNA vaccines. https://www.science.org/doi/10.1126/sciimmunol.ade2798

Novavax, likely because its stimulation method is slow and steady, instead of creating a hot and heavy pseudoinfection in your muscles like RNA, does not induce the IgG4 isotype switch. It instead generates more IgG3, with the most Fc effector function. https://www.journalofinfection.com/article/S0163-4453(24)00053-7/fulltext

So those are the 3 differences between Novavax and RNA: (1) CTL responses with RNA, (2) higher peak Abs with RNA, (3) faster conversion to non-catalytic IgG4 with RNA. Actually there's a fourth: Side effects are stronger with RNA than Novavax. Essentially the headache and fatigue we get from RNA vaccines is quite a bit out of line compared with historical flu vaccines, whereas Novavax is more in line with flu vaccines (not surprisingly, as both use proteins). Here's one study; there are others: https://www.mdpi.com/2076-393X/12/7/802

So for those of use who have been following the development of RNA vaccines and watching the Novavax tortoise moving toward the finish line, the major difference has always been clear: RNA vax provide a strong stimulus, stronger than what we are used to in annual vaccines.

Without a doubt, for the initial rounds of vaccination in 2020 and 2021, RNA was a lifesaver. The higher reactogenecity was a small price to pay to avoid hospitalization. Issues with vaccine purity delayed Novavax, so we were lucky to have RNA ready. 

However, now that we are getting into these 3- to 6-month long waves, now that nearly everyone has had COVID-19 and therefore has hybrid humoral and cellular immunity, we can rethink which kind of vaccine is appropriate on an annual basis. 

Essentially now we are fighting off a chronic threat of COVID19. Vaccines are really not effective enough to be the only preventive measure. We'd have to get vaxxed 4 times a year, which is not going to happen. Instead we have to figure out our own behavioral risk/reward ratios. 

For preventing transmission, the situation is similar to flu (a poor analogy as SARSCoV2 outcomes can often be more severe than flu). Perhaps the best we can do is avoid spending too much time in loud crowded indoor setting, and encourage people to test at the first symptoms.

So the vaccines now become a personal choice, and there is no right or wrong answer. But given the differences presented above, my own plan is to get 2 years Novavax (slow and steady baseline) and 1 year Pfizer-BioNTech (for a little CD8 T cell push).

If in a given year, we have a tightly timed surge for just 2 month (say Dec-Jan), then RNA may be worth considering, but that doesn't seem to be happening this year. So might was well do the lesser insult of protein, riding with the tortoise instead of the hare.

That's just me. Not medical advice. YMMV. This is essentially a willingness to take on slightly higher integrated risk of infection for a more balanced immune system.

Forgot to mention, there's a formulation difference between the JN.1 Novavax and the KP.2 Pfizer and Moderna. At the VRBPAC meeting, Novavax made a point that JN.1 was the father to all circulating strains and the antigenic differences were minor compared to the leap from XBB. 

This sounded reasonable to me at the time, because in protein evolution we always evolve on the latest two generations in case the latest one becomes an evolutionary dead-end. The VRBPAC agreed with Novavax, which was why their recommendation was anything in JN.1.

Everyone thought that was settled, except the next day, FDA (withouth asking VRBPAC) announced they would prefer KP.2 which was the rising sublineage at the time. Pfizer and Moderna (who had presented results of KP.2 boosters to VRBPAC) immediately said they'd do it. Hmm, I wonder who might have called their contacts at FDA? But now KP.3 is the one going around. And Novavax's data are that their JN.1 vax neutralizes KP.3 well. Even Moderna shows JN.1-to-KP.3 is better than KP.2-to-KP.3. So Novavax was right.

https://x.com/JUurinmaki/status/1825034073690997055

BTW here's the adverse effect (AE) difference between RNA COVID-19 vax and seasonal influenza vax (SIV), which are protein vax. RNA vax has ~2x higher rates of adverse effects than flu vax. And earlier we saw RNA vax has 2x higher AEs than Novavax. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2809119

I've read it asserted in the literature that RNA vax reactogenicity is similar to seasonal flu vax; this is simply not true. Novavax and seasonal flu vax, however, are similar in reactogenicity, as expected as they are similar in mechanism.  

BTW the paper above concluded adding flu to RNA vax doesn't increase reactogenicity, basically assuming readers are taking the RNA vax anyway. But the more interesting comparison is how RNA vax and flu vax compare. The paper never discusses the unfavorable result.

https://www.science.org/doi/10.1126/sciimmunol.adg7327

And here's a thread on RNA-induced IgG4, by the scientist who discovered it. He said harms are unknown, which is still the case, but he believed we didn't have to worry as he couldn't see a need for annual RNA boosters! Maybe reasonable to be cautious. https://threadreaderapp.com/thread/1606002981513662478.html

Also Moderna causes more IgG4 switching than Pfizer-BioNTech, as expected for its larger dose of RNA, eliciting of higher Ab levels, and stronger side effects. So everything correlates.

[mostlysignssomeportents]

The public paid for "Moderna's" vaccine, and now we're going to pay again (and again and again)

Moderna is quadrupling the cost of covid vaccines, from $26/dose to $110–130. Moderna CEO Stephane Bancel calls the price hike “consistent with the value” of the mRNA vaccines. Moderna’s manufacturing costs are $2.85/dose, for a 4,460% markup on every dose:

https://arstechnica.com/science/2023/01/moderna-may-match-pfizers-400-price-hike-on-covid-vaccines-report-says/

If you’d like an essay-formatted version of this thread to read or share, here’s a link to it on pluralistic.net, my surveillance-free, ad-free, tracker-free blog:

https://pluralistic.net/2023/01/24/nationalize-moderna/#herd-immunity

Now, obviously the manufacturing costs are only part of the cost of making a vaccine: there’s also all the high-risk capital that goes into doing the basic research. Whenever a pharma company like Moderna hikes its prices, we’re reminded that the rewards are commensurate with these risks.

But the story of the Moderna vaccine isn’t one of a company taking huge gambles with shareholder dollars. It’s the story of the US government giving billions and billions of dollars to a private firm, which will now charge the US government — and the American people — a 4,460% markup on the resulting medicine.

Writing for The American Prospect, Lily Meyersohn reminds us of the Moderna vaccine’s origin story: the NIH spent $1.4B developing the underlying technology and then the US government bought $8b worth of vaccines at $16/dose, giving Moderna a guaranteed 460% margin on each jab:

https://prospect.org/health/2023-01-23-moderna-covid-vaccine-price-hike-bernie-sanders/

Moderna clearly does not feel that the billions it received in public funds came with any obligation to serve the public interest. The company falsified its patent applications, omitting the NIH scientists who co-developed the vaccine, claiming sole ownership:

https://blog.petrieflom.law.harvard.edu/2022/01/06/nih-moderna-mrna-covid-vaccine-patent/

As Meyersohn writes, this omission allows Moderna to block the NIH from licensing the vaccine to foreign manufacturers — including vaccine manufacturers in the global south, home to many powerhouse producers of vaccines:

https://pluralistic.net/2022/08/24/waivers-for-me-not-for-thee/#vaccine-apartheid

Moderna claims to have capitulated to the NIH on the patent question, but it’s a lie — even as they were publicly announcing they would drop their bid to exclude NIH scientists from their patent application, they quietly filed for a continuance that would let them renew their exclusive claim later, when the heat has died down:

https://www.nytimes.com/2021/12/17/us/moderna-patent-nih.html

This maneuver, combined with Astrazeneca reneging on its promise to open its vaccine — a move engineered by Bill Gates — has deprived billions of the world’s poorest people of access to vaccines. Many of these people were previously blocked from accessing AIDS drugs when the Gates Foundation teamed up to block WTO vaccine waivers:

https://pluralistic.net/2021/04/13/public-interest-pharma/#gates-foundation

These immunucompromised, unvaccinated people are at increased risk of contracting covid, and when they do, they are sick for longer, creating more opportunities for viral mutation and new, more virulent variants.

That was where we stood before Moderna announced its 400% vaccine price-hike. Now, millions of Americans will also be blocked from accessing vaccines, opening the door for rampant, repeated infections, more mutations, and more variants. As Alex Lawson of Social Security Works told Meyersohn, at that price, the US will not be able to achieve herd immunity.

What will Moderna do with the billions it reaps through price-gouging? It won’t be research. To date, the company has spent >20% of its covid windfall profits on stock buybacks and dividends, manipulating its stock price, with more to come:

https://www.levernews.com/how-big-pharma-actually-spends-its-massive-profits/

It’s not an outlier. Big Pharma is a machine for commercializing publicly funded research and then laundering the profits with financial engineering. The largest pharma companies each spend more on stock buybacks than research:

https://www.levernews.com/how-big-pharma-actually-spends-its-massive-profits/

Moderna didn’t have a single successful product for its first decade of operation: it is only a going concern because it got billions in free public research and billions more in public commitments to buy its products at a huge markup.

It wasn’t always this way. Until the 1990s, pharma companies that commercialized public research were bound to license terms that required “reasonable pricing.” NIH inventions were subject to non-exclusive licensing terms, ensuring a competitive market.

The NIH could act to stem Moderna’s profiteering. Moderna’s vaccine (like virtually all mRNA vaccines) uses NIH patent 10,960,070 — though Moderna doesn’t license the ‘070 patent. The NIH could use the threat of a patent infringement suit to force Moderna to put pandemic resilience and access to vaccines over financial engineering and executive bonuses.

When it comes to patent enforcement to protect the public interest, the USG has a long history of channeling King Log, letting companies price-gouge with products built on public research.

https://media.nature.com/original/magazine-assets/d41586-021-03535-x/d41586-021-03535-x.pdf

The states are stepping in where the feds have failed to act, spinning up their own pharma production capacity to create a “public option” for medicine — think of California’s move to produce insulin and other meds:

https://prospect.org/health/its-time-for-public-pharma/

Or Massachusetts’s MassBiologics, the “only non-profit, FDA-licensed manufacturer of vaccines” in the USA, which sells its generic tetanus and diptheria vaccines nationwide:

https://www.umassmed.edu/massbiologics/

The US has a long way to go when it comes to using public production to offer competitive discipline to private pharma. Sweden nationalized its pharma in 1970. Cuba got there in 1960, and is a pharma powerhouse:

https://pluralistic.net/2021/11/28/somos-cuba/#omishambles

Meyersohn closes her excellent article with a warning and a promise: though public covid vaccines are a long way away, new vaccines for RSV and even cancer are in the pipeline, and without “substantial intervention,” Moderna will be a “harbinger…of crises of inequitable access to come.”

[Image ID: Moderna headquarters in Cambridge, Mass. On the left side of the entry, a Jacobin with a guillotine gets ready to decapitate an aristocrat. On the right side of the frame, a cigar-chomping, top-hat wearing ogrish figure makes ready to yank a gilded dollar-sign lever while holding an MRNA molecule disdainfully aloft]

[a-typical]

What’s the difference between Pfizer/BioNTech, Moderna, and Novavax COVID-19 vaccines?

The Pfizer-BioNTech and Moderna COVID-19 vaccines use mRNA as the active ingredient. The mRNA is converted by our cells into the antigen, in this case, the spike protein of SARS-CoV-2.

The vaccine contains the mRNA, which is synthesized in the lab using a DNA template, the building blocks of RNA, and the enzyme that puts those building blocks together into the right order. mRNA is the molecule template for every protein in every organism. The mRNA sequence is a code for our cells to link amino acids together into functional proteins

mRNA is very fragile, so it is encased in a lipid nanoparticle (LNP) that protects it until it gets into our cells. When the vaccine is administered, the mRNA is released and is used to synthesize the spike protein which is displayed by cells that produced it. That spike protein is recognized by our innate immune cells like dendritic cells and macrophages as well as B cells, which initiates immune response and generation of memory immunity.

In contrast, Novavax is a protein-based vaccine, which contains the prefabricated antigen - the spike protein - instead of the template for it. To make the antigen, we turn cells into protein-producing factories in the lab.

Novavax uses Sf9 cells (moth cells) infected with an insect-specific virus that has been genetically engineered to contain the gene for the spike protein of SARS-CoV-2. These viruses will hijack the cellular machinery of the Sf9 cells to produce lots of spike proteins and baby viruses. Those will continue to reproduce and produce proteins, which will be harvested, purified, and formulated with the other ingredients in the final vaccine.

When the vaccine is injected, the antigen will be recognized by the same innate immune cells listed above, which will trigger the same immune response pathway.

While the vaccines use different technologies, ingredients, and manufacturing processes, the immune responses center around recognition of the spike protein and generating adaptive immune responses targeting that antigen.

[major-x-blog]

Ma Nooooooo, Ma Quale complotto, ma quale depopolamento, ma quale Agenda 2030....... Anche Questa è unaltra Tacca sul Bastone, Peró i NO VAX sono il Vero Problema da sconfiggere, vero??????

Certo visto che i No Vax hanno cervello da Vendere, non come le pecore al pascolo per brucare il "Sacro Siero" Detto anche ARMA CHIMICA!!!!!

se anche stavolta non vi sarà chiaro.......

CAZZI VOSTRI...... 🖕🖕🖕🖕🖕🖕🖕

[ireton]

 DISCLAIMER: Please do your own research and come to your own conclusions.

Canadian pharmaceutical companies Arbutus and Acuitas, as well as American pharmaceutical companies Pfizer and Moderna, the University of British Columbia & Anthony Fauci connection.

[diablo1776]

"Safe and Effective" they say..

Go follow @DiedSuddendly_ on Twitter. It's pretty unbelievable, unfortunately.

[tomorrowusa]

The spy balloon isn’t hugely significant on its own, but it adds to the sense that Beijing’s competence has been exaggerated.

David Leonhardt at the New York Times.

There’s been a lot of hype regarding China this century. But a number of its actions suggest that its success has been overstated.

China is a totalitarian state. The government tries to micromanage the lives of its citizens. The way it handled the COVID-19 pandemic was an avoidable disaster.

The Chinese government foolishly refused to use mRNA vaccines produced in Europe and North America. Its own homemade vaccines were less effective and required the draconian “zero COVID” policy to keep the virus from spreading.

This article may explain why the Chinese government failed to effectively vaccinate its population when it could easily afford to.

Moderna refused China request to reveal vaccine technology, Financial Times reports

China has had a policy of forcing foreign companies to share their tech secrets as a prerequisite for doing business in China. Western businesses, salivating at the thought of massive profits on the mainland, mostly agreed. China was probably able to gather more tech know-how this way than through industrial espionage and hacking.

So Moderna (and likely BioNTech & Pfizer) wisely refused to hand their intellectual property over to the Chinese authorities. So the only people in China who eventually received the mRNA vaccines were foreign nationals who lived in the country.

As I noted a minute ago, China can easily afford the Moderna and Pfizer-BioNTech vaccines but the government has refused to import them because the companies would not submit to tech extortion.

When China’s zero COVID policy abruptly ended, the longstanding effort to extract intellectual property from the West severely backfired. Many of China’s top scholars, scientists, and intellectuals were among the numerous COVID-19 fatalities. It’s true that they were mostly elderly, but many still had years of productivity ahead of them.

In China’s Covid Fog, Deaths of Scholars Offer a Clue

Those are just the more famous ones. There are probably many additional less well-known scientists who died in recent months.

So the Chinese government is not only less competent than it would like the world to believe but it is also less competent than many anti-Chinese politicians in the West would like to have us believe.

[agreenroad]

Moderna Shuts Down mRNA RSV Vaccine Trial in Babies After Shots Linked to Severe Side Effects, FDA Document Reveals

Moderna Shuts Down mRNA RSV Vaccine Trial in Babies After Shots Linked to Severe Side Effects, FDA Document Reveals

[pandemic-info]

https://twitter.com/jeffgilchrist/status/1700854098755563660

#Novavax vs mRNA vaccine This thread explains how @Novavax is different from the #Moderna and #Pfizer #mRNA #vaccines and describes some of the benefits such as broadened #variant recognition, more durable #immunity, and fewer side effects.

This is an awesome thread explaining all of the above + recommendations for primary layers of protection like ventilation, filtration, and masking.

Notable:

What about people who had mRNA doses previously but want to consider Novavax? There have been several studies now that found mixing the two, getting mRNA and then Novavax actually gave better results than just mRNA on its own.

One study found that getting Novavax as a booster after mRNA "may enhance the persistence and durability of vaccine-mediated immunity compared to mRNA options" ...with slower decay rate compared to an mRNA booster dose and less side effects than mRNA boosters

While vaccines are important, they should be the last layer of protection to rely on in case all the other layers fail and you get exposed. Vaccines should not be the one and only layer governments all seem to be currently relying on.

This link may be easier to read:

[somosprojetoamigos]

Vacina contra câncer de pele está nos últimos testes: veja quem vai poder tomar

Em Londres, uma vacina “personalizada” contra o câncer de pele começou a ser testada em voluntários com melanoma, a forma mais letal desse tipo de câncer, e está na última fase de testes clínicos antes de passar pela aprovação de órgãos reguladores. A produção das vacinas está sendo feita pela farmacêutica Moderna em conjunto com a Merck Sharp and Dohme (MSD). De nome técnico mRNA-4157 (V940), o…

[didanawisgi]

mRNA influenza vaccine