Bad flu shots and worse: self-amplifying mRNA for vaccines and drugs

For the tidy sum of $499.00, you can buy the STAT report on the future of mRNA drugs and vaccines. Below is a free teaser from the report, written by a Stanford PhD who still gets some important things wrong, such as his second sentence. The mRNA has been found months later in some peoples’ blood and tissue.

I am posting this mainly to warn readers thatthe mRNA platform, which has given us so-called vaccines that are a disaster, and which after a few months increase your susceptibility to COVID (the negative efficacy problem that occurs after 2 months in 5-11 year olds and after 6-8 months in adults) is being expanded to produce not only vaccines, but also drugs.

The final paragraph below tells you that an Australian company, CSL Sequirus, will license the technology to you for a tidy sum starting at $200 million. This company was Commonwealth Serum Labs once and was owned by the Aussie government; in fact, I remember CSL in Canberra in the 1970s. It becameprivatized in 1991.Somehow. I just realized that the word pirate is buried in privatized. CSL acquired Novartis’ failing vaccine business and is now in Cambridge MA, a short walk from where I went to college, and it supplies flu vaccines to the US market and beyond.

And it just acquired a self-amplifying mRNA technology from Arcturus, one of the Canadian companies responsible for the LNP technology for COVID vaccines.

01 Nov 2022

King of Prussia, PA – 01 November 2022 –CSL Limited (ASX:CSL; USOTC:CSLLY) today announces that its subsidiary, CSL Seqirus, has entered into a collaboration and license agreement with Arcturus Therapeutics Holdings Inc (“Arcturus Therapeutics”) to access their late stage self-amplifying mRNA (sa-mRNA) vaccine platform technology.

CSL-Sequirus makessome of the worst flu vaccines available:

Fluadcontains the MF59 adjuvant that Novartis counted on, then dumped—which can dangerously overcharge your immune system leading to autoimmune disease. The MF59 squalene adjuvant seems to change hands every few years. It is recommended for the elderly in whom the dread side effects are believed to occur less often. It has shown no benefit over ordinary, unadjuvanted flu shots, only more side effects.

Fluad is [criminally] licensed for babies 6 months-2 years old in Canada, which Idiscussed in my testimony to the New Brunswick legislaturein 2019, though it was never shown to be either safe or effective, and presumably a lot of money changed hands to get it into Canadian babies.

Fluad has had “229 million doses distributed over 20+ years.” That tells you it is a failed product: despite having obtained licenses in over 30 countries, only about 10 million doses per year have been sold.

And the CDC’s vaccine advisory committee ACIP, which in October put COVID vaccines on the childhood schedule,recommends Fluad preferentially for seniors—which should be a red flag to avoid it.

MF59 was firstowned by Sclavo, an italian company, which managed to get it licensed for a flu shot in Italy in 1997. Then bought by Chiron, then taken over by Novartis in 2006. And now it belongs to CSL-Sequirus. Because apart from the flu shot, it never went anywhere.

Flucelvax is the only flu shot grown in dog kidney cells. If this was such a great technology, why is it used so rarely? Yet last year these flu shots were approved for US babiesfor the first time.

Afluria® Quadrivalent | Inactivated Quadrivalent Influenza Vaccine (split viron)
Also marketed as Afluria® Quad and Afluria® Tetra in various different markets. Afluria® | Inactivated Influenza Vaccine (split viron)
Also marketed as Enzira®, Fluvax® and Nilgrip® in various different markets. Agrippal® | Influenza Vaccine (surface antigen inactivated)
Also marketed as Begripal®, Fluazur®, Sandovac®, Agriflu®, Chiroflu® in various different markets.

Fluad® | Inactivated Influenza Vaccine, Adjuvanted
Also marketed as Chiromas® in Spain. Fluad® Pediatric | Inactivated Influenza Vaccine, Adjuvanted Fluad® Quadrivalent | Inactivated Quadrivalent Influenza Vaccine, Adjuvanted
Also marketed as Fluad® Quad and Fluad® Tetra▼ in various different markets.

Flucelvax® Quadrivalent| Inactivated Influenza Vaccine

mRNA drugs with a built-in ‘copy machine’ could lead to safer, more effective therapies

By Jonathan Wosen Nov. 18, 2022

Remember that messenger-RNA-based Covid-19 vaccine you got? Just a few days later, the teeny molecular messengers contained in the shot were already gone.[Don’t I wish it were true.—Nass]

Despite scientists’ best attempts to bolster mRNA and improve its stability, these molecules are ephemeral.[Read: there is a lot of degraded mRNA material in each vial and we don’t know what it does to your body—Nass.]

That’s not necessarily a bad thing. A short, sharp burst of protein can be enough to rev up an immune response. And for gene therapies, the brief lifetime of mRNA is a major plus — you wouldn’t want DNA-cutting enzymes running rampant in your cells after they’ve already made a helpful genetic edit.

In some cases, however, a patient might need to produce high levels of a therapeutic protein for a prolonged period of time to benefit from a treatment. And reaching those levels with current mRNA technology isn’t always feasible. [Exactly: it is a crap shoot how long the mRNA continues to be translated into protein products and what happens to all the untranslated bits of microRNA.—Nass] That’s because while repeatedly injecting high doses of mRNA into mice might look good in the lab, the benefits often show up only at doses so high that they wouldn’t be safe in people.

“For the field of mRNA, one of the big white whales for a long time is protein drug replacement,” said Nathaniel Wang, CEO of Replicate Bioscience.

Wang’s company is among those devising a workaround for this problem: messenger RNA that makes more of itself once it is taken up by cells. This may sound improbable, but so-called self-replicating RNA works because the mRNA molecule doesn’t just code for a therapeutic protein. It also codes for proteins normally found in viruses which allow them to copy their RNA genomes once they’ve slipped inside a cell.

In effect, self-replicating mRNA comes with its own copying machine.

The result is the production of molecules that can last for up to around two months in the body, according to initial laboratory studies, suggesting that these therapies could achieve effects that would otherwise take roughly 1,000 times the dose of non-replicating RNAs. The potential benefits, Wang said, are twofold: Administering low doses could make these therapies safer, and they could allow researchers to divvy up a given batch of therapeutic mRNA among more patients who are in need.

But it’s a strategy that also comes with its own challenges, as a new STAT Report explains. Self-replicating mRNAs are longer than regular mRNAs because of the self-copying machinery they encode — they can stretch up to 16 kilobytes compared to a couple of kilobases for non-replicating mRNA. At that point, simply keeping the molecule together isn’t easy.

“The manufacturing challenge of having a product that has good integrity and good potency and purity” is potentially more of an issue for these larger RNAs, said Jeffrey Ulmer, who has been working in the field for 30 years and is a consultant and adviser to Replicate and several other mRNA companies.

Still, Replicate has managed to synthesize mRNA of up to 16 kilobases after tweaking its manufacturing process. The San Diego company, launched in February 2020, has raised about $53 million. It is now working on a treatment for patients with estrogen-receptor positive breast cancer who have developed resistance to hormone-targeted therapies, resulting in cancer cells metastasizing throughout the body. Another one of the company’s oncology treatments encodes immune cytokines and proteins meant to make tumors more responsive to immune attacks.

Replicate is also developing self-replicating mRNA to treat inflammatory and autoimmune disorders like arthritis and colitis, by encoding proteins that essentially soak up inflammatory cytokines. Wang said that the company aims to get at least one of these drugs into clinical trials in 2023.

Another San Diego biotech, Arcturus Therapeutics, is focused on a different use of this technology: vaccine boosters. The reason, explained Arcturus CEO Joseph Payne, is that a tiny bit of self-amplifying mRNA could go a long way toward reigniting the body’s immune responses by restimulating these cells with high levels of a viral protein.

It’s a strategy that Arcturus, a publicly traded biotech founded in 2013, is testing with a self-replicating Covid-19 vaccine that is currently in clinical trials. And in mid-August, Arcturus reported data indicating that clinical trial participants who’d received the company’s vaccine as a booster still had high levels of antibodies that could block Omicron variant BA.5 six months after getting the shot.

In the long run, Payne said, he thinks self-replicating mRNA could also allow researchers to develop mRNA therapies that aren’t feasible right now.Some of the proteins in your cells last several days, while others last less than an hour. And producing a protein that’s going to break down almost immediately isn’t much help unless you can keep churning out new copies. That’s why current mRNA therapies work best for longer-lasting proteins. But having a self-copying pool of mRNA could allow cells to continue to churn out proteins that are both ephemeral and important.

The technology is drawing financial interest. Arcturus recently struck a deal with Australian life science company CSL Seqirus licensing its self-amplifying technology for an upfront payment of $200 million and, potentially, $4.3 billion in future milestone payments.

“It’s still challenging, it’s still very early,” Payne said. But, he added, “We’re really excited about that part of our pipeline.”