mRNA: Vaccine or Gene Therapy? The Safety Regulatory Issues

Int. J. Mol. Sci. 2023, 24(13), 10514; https://doi.org/10.3390/ijms241310514

Received: 9 June 2023 / Revised: 19 June 2023 / Accepted: 21 June 2023 / Published: 22 June 2023

Abstract

COVID-19 vaccines were developed and approved rapidly in response to the urgency created by the pandemic. No specific regulations existed at the time they were marketed. The regulatory agencies therefore adapted them as a matter of urgency. Now that the pandemic emergency has passed, it is time to consider the safety issues associated with this rapid approval. The mode of action of COVID-19 mRNA vaccines should classify them as gene therapy products (GTPs), but they have been excluded by regulatory agencies. Some of the tests they have undergone as vaccines have produced non-compliant results in terms of purity, quality and batch homogeneity. The wide and persistent biodistribution of mRNAs and their protein products, incompletely studied due to their classification as vaccines, raises safety issues. Post-marketing studies have shown that mRNA passes into breast milk and could have adverse effects on breast-fed babies. Long-term expression, integration into the genome, transmission to the germline, passage into sperm, embryo/fetal and perinatal toxicity, genotoxicity and tumorigenicity should be studied in light of the adverse events reported in pharmacovigilance databases. The potential horizontal transmission (i.e., shedding) should also have been assessed. In-depth vaccinovigilance should be carried out. We would expect these controls to be required for future mRNA vaccines developed outside the context of a pandemic.

https://www.mdpi.com/1422-0067/24/13/10514

>>19109977

Conclusions

Although the principle of action of COVID-19 mRNA vaccines corresponds to the definition of gene therapy products (GTPs), they have been excluded from the regulation of GTPs by the regulatory agencies (US-FDA and EMA) and subjected to the regulation of vaccines against infectious diseases. No scientific or ethical justification is given for this exclusion, and there remain inconsistencies in the regulations. For example, under European and French regulations, a vaccine must contain an antigen, which is not the case for mRNA vaccines. These products could be considered “pro-vaccine”. In fact, mRNA vaccines do not contain an antigen, but make the vaccinee produce it. They can therefore be classed as pro-drugs or “pro-vaccine”. Special regulations should be drawn up for this type of product, insisting on potency controls, i.e., the quality, quantity, duration and sites of expression of the antigen of interest, as well as the toxicity of this antigen. As proposed at the start of 2020, the SARS-CoV-2 spike protein interacts with the renin-angiotensin system [101,102,103] and has a recognized toxicity that was known since before COVID-19 [104] and has been confirmed since [105,106,107,108].

According to European regulations, vaccines are human medicinal products and must therefore undergo the same controls, but not all of these controls are generally applied to vaccines against infectious diseases. With regard to the controls applied to mRNAs, it is worth noting that the degree of purity of the product is lower than that required for any drug: this is questionable for a new formulation and principle of action. It is also possible that batch heterogeneity was not detected by the batch release procedure. Impurities linked to this new formulation could pose safety problems; the presence and quantity of contaminating DNA from the template used to manufacture the RNA and of ds-RNA would need to be reassessed. The presence of antibiotic resistance genes in contaminating template DNA also raises safety issues.

Pharmacokinetic studies are not generally required for vaccines, except in the case of new formulations, which is the case here. However, extensive studies in this field would have been necessary, since they did not detect the wide distribution and persistence of mRNA, and its product, the spike protein, in the bodies of vaccinees, the passage of mRNA in breast milk, nor the possible passage through the placenta of vaccinated mothers. GTP regulations require these in-depth studies on the complete formulation (the lipid nanoparticle loaded with the mRNA corresponding to the drug product).

Because of this wide and persistent biodistribution, essential tests required for GTPs should have been carried out regarding: the risk of genotoxicity, genome integration and germ-line transmission, insertional mutagenesis, tumorigenicity, embryo/fetal and perinatal toxicity, long term expression, repeated toxicity and excretion in the environment (shedding in the seminal fluid, for example).

cont..

>>19109979

The long-term safety monitoring of GTPs is required over several years whereas, for vaccines, it is generally only carried out over a few weeks. This should not be acceptable, given the persistence of the drug product and the expressed protein. The known results of anti-cancer therapies and mRNA vaccines could lead us to anticipate problems of safety and efficacy. In the case of anti-cancer mRNAs, the vast majority of open-label clinical trials have been carried out on very small numbers of patients, with either unpublished or negative results [109,110]. Randomized studies also showed negative results, reporting more frequent adverse events in the treatment group [111,112]. Concerning infectious diseases, two trials of mRNA vaccines encapsulated in LNPs showed notable adverse effects. A trial of an mRNA vaccine against rabies showed numerous adverse effects superior to those of the classic vaccine, which is already very reactogenic, notably lymphopenia (this effect was also found for anti-COVID-19 mRNA vaccines) [113]. An influenza vaccine trial [114] showed severe adverse effects in humans (31 subjects were observed over only 43 days and at least 4 serious adverse effects were found). In a non-randomized trial against HIV [115], the response was inexplicably incomplete in some patients. According to another HIV trial of 15 participants against a placebo, immune responses were unsatisfactory and of limited duration [116]. The founder of BioNTech himself, Ugur Sahin, warned against the use of codon optimization, which can alter translation speed and lead to misfolding. He also underlined the potential toxicity of unnatural nucleotides. He also mentioned the wide biodistribution of mRNA injected intramuscularly. He reminded us that we should fear the appearance of anti-self mRNA antibodies in patients suffering from autoimmune diseases [27].

The role of regulatory agencies is to ensure the safety and efficacy of medicines. The COVID-19 pandemic emergency has accelerated the timetable for the production and clinical use of COVID-19 vaccines; it is, therefore, possible that certain safety aspects have not been fully addressed. It is, therefore, important to take these aspects into account in the future, so as not to undermine public confidence in vaccines in general.

The WHO declared an end to the emergency phase of the COVID-19 pandemic at the beginning of May 2023 but will continue to authorize the use of the Emergency Use Listed (EUL) procedure. The emergency authorization of vaccines should be transformed into prequalification via a smooth transition [117]. However, a wide-ranging public discussion should be opened on this transition to the routine use of mRNA vaccines, without them being subject to the controls required for GTPs.

In the EMA document designed to regulate the clinical evaluation of new vaccines from 2023, there is no mention of mRNA vaccines, and it is still specified that vaccines contain antigens; this document would therefore not apply to mRNA vaccines that do not contain antigens. It is once again specified that nonclinical pharmacokinetic studies might be applicable when new delivery systems are employed or when the vaccine contains novel adjuvants or excipients. It is a pity that these points have not been specified specifically for mRNA vaccines [118]. An article from early 2021 [119] emphasized the need for further studies to ensure the quality, efficacy and safety of mRNA vaccines; it was written before these products were marketed. It seems important to clarify which additional controls should be required in light of the detailed results of the preclinical trials and safety data published in the post-marketing phase.

In the future, it should be discussed whether all mRNA-based products should be subject to the same regulations and controls, whether or not they are considered vaccines. It is not justifiable to subject therapeutic mRNAs to strict controls when they are intended for patients representing a small proportion of the human population, and to exclude from these controls mRNA vaccines intended for the majority of the healthy human population.

>>19109974

THEY hate you for it more. We in good company though.

John 15:18

>>19110045

aspertame diet coke

>>19110058

selling data, just like any other site or browser. who like what, how much time spent, when where what triggers most likely to result in time spent, etc

easy way to find new politricksters and people in key positions to blackmail or further bait with their proclivities.

and sales or rentals of people and children most likely

>>19110081

>church going Christians

oxymoronical phrase like

virtually spotless

smart bomb

etc

Jesus neither built nor attended any physical church. You are the temple.

Not a 501c3 govt sponsored brainwashing and intel scraping facility of deceit, hypocrisy, whoredom, and jezebel spirit.

What better establishment to be an intelligence gathering hub than a tax exempt church where people trust initiates with their secrets?

COOHMP

>>19110088

why isn't woods standing w people like

Rick Schroder

Kevin Sorbo

Jim Caviezel

Elijah Wood

etc…

he doesn't know? pfft… uh huh

>>19110128

https://www.thedailybeast.com/showbiz-kids-exposes-hollywoods-pedophilia-epidemic

The New Film Exposing Hollywood’s Child-Abuse Epidemic

“Pretty much all of the young men were abused in some way, sexually,” says Evan Rachel Wood in “Showbiz Kids,” a disturbing new HBO documentary premiering July 14.

Published Jul. 10, 2020 4:43AM EDT

While fame and fortune are an ever-enticing dream, few things seem less appealing than being a child star, and HBO’s Showbiz Kids (premiering July 14) certainly reinforces that feeling. Awash in anecdotes about the ways in which the industry—and the attendant hunger for the spotlight that consumes both children and parents—warps, alienates and exploits kids, it’s a documentary which illustrates that, sometimes, being nobody is far healthier, and more fulfilling, than being well-known.

Sexual misconduct is the dark cloud hovering over Showbiz Kids, and it comes to the fore when former Diff’rent Strokes star Todd Bridges recalls being molested as a child—a disclosure that, according to Evan Rachel Wood, isn’t unique, as she claims, “In my experience, I know a lot of kids that grew up in the industry. And what surprised me when I got older was finding out that pretty much all of the young men were abused in some way, sexually.” She then relays that, at a recent Golden Globes gala, she watched a pedophile (whom she doesn’t name) win an award, and had to walk out because she was so disgusted by the praise being lavished upon this monster. As she departed, she thought to herself, “I don’t know if I can do this anymore. I can’t keep watching this happen. I don’t know how to handle this. This has to stop.”

Those moments are definitely the ugliest, and most eye-opening, in Showbiz Kids. Written and directed by Alex Winter, whose big breaks came in Joel Schumacher’s 1987 Brat Pack vampire thriller The Lost Boys and 1988’s Bill & Ted’s Excellent Adventure, the film knows whereof it speaks. An opening photo montage of illustrious young luminaries, from Shirley Temple and Mickey Rooney to Ron Howard, Drew Barrymore, and Mary-Kate and Ashley Olsen, climaxes with a portrait of Winter himself, thereby underlining that this project is not only near and dear to his heart, but one driven by first-hand knowledge of the kinds of ups and downs endured by its marquee subjects.

Considering Winter’s familiarity with this topic, it’s mildly disheartening that Showbiz Kids isn’t more personal; although the actor has worked in the business for more than three decades, and admitted in 2018 that he suffered “hellish” sexual abuse at the hands of an adult man during the 1970s, his own experiences are conspicuously absent from these proceedings. Such reserve is in keeping with the overarching nature of his documentary, which largely avoids tabloid-y tales, and Winter’s reticence on that front comes across as being motivated by respectfulness. Yet it also makes Showbiz Kids seem like it’s pulling its punches—an impression exacerbated by the fact that, when it does touch upon the nasty side of the industry for pint-sized performers, it does so only fleetingly.

That’s most apparent in the case of Bridges. Though he didn’t die of an overdose like his Diff’rent Strokes co-star Dana Plato, Bridges’ drug addiction made for sensationalistic headlines, as did his multiple run-ins with the law—including being charged, and acquitted, of killing his dealer. Nonetheless, those incidents are cursorily addressed, as if the film were afraid that delving too deeply into such muck might reconfigure the material as a cautionary tale. Many of its speakers candidly discuss their struggles grappling with their new celeb-reality, but there’s a sense here that everyone is hesitant to truly decry a system that spits up and chews out kids with startling rapidity, and with little regard for the emotional and psychological scars it leaves behind.

Still, if uninterested in picking at old scabs, Showbiz Kids doesn’t wholly shy away from the unseemly. With notable distress in her eyes, Wood discusses being pushed into the profession by an artistic clan, and how her success compelled her to silence herself, since she believed that any complaints would be viewed as ingratitude by friends and family. Both Wil Wheaton and Milla Jovovich confess that they too were thrust into acting by mothers who sought to fulfill their own aspirations through their kids. And Henry Thomas remembers the intense social ostracization he suffered in his San Antonio hometown after E.T. became a global phenomenon, and how he was later squeezed out of the business as a teen when casting directors decided he’d outgrown his appeal.

p1

>>19110146

“That footage, along with publicity photos, conveys the strangeness of child stardom, where kids unnaturally primp and pose for the camera—as Jovovich did in sexualized modeling shoots that she astutely states would never be allowed today.”

Bolstering these accounts is a collection of excellent behind-the-scenes clips and audition videos, including the teary-eyed tryout that nabbed Thomas his role in Steven Spielberg’s sci-fi classic. That footage, along with publicity photos, conveys the strangeness of child stardom, where kids unnaturally primp and pose for the camera—as Jovovich did in sexualized modeling shoots that she astutely states would never be allowed today. It’s too bad, then, that Showbiz Kids often just skims the surface. Jada Pinkett Smith briefly opines about helping her kids Jaden and Willow navigate modern fame, and the late Cameron Boyce reflects on transitioning into adulthood after being raised in a bizarre, hyper-coddling Disney bubble. Those and other intriguing threads (like the impact social media has on current kid stars) are raised only to be promptly dropped for the next mildly interesting story.

Showbiz Kids also follows two aspiring kid stars—Orlando native Marc Slater, who along with his mom travels to Los Angeles for pilot season; and New Yorker Demi Singleton, a vet with Broadway’s School of Rock and The Lion King on her résumé—as they search for the gig that will forever transform their fortunes. Their plights don’t reveal much, other than that striving for stardom means sacrificing much of what constitutes a normal life, as Demi learns when her summer sleepaway camp plans are shelved for additional auditions. Whereas in-depth portraits of these two might have provided a new perspective on this surreal career path, what’s presented is short on revelatory insights.

In Showbiz Kids’ best archival clip, young Mara Wilson (Mrs. Doubtfire, the 1994 Miracle on 34th Street remake, Matilda) loses her tooth during a TV interview, and the look of surprise, horror and fear that washes over her face speaks volumes about the crushing expectations put upon kid actors. That pressure is addressed more overtly in many of its one-on-one chats—including by Wilson herself, who appears to have emerged on the other side of her Hollywood tenure as a happy and well-adjusted adult—but never more powerfully than in that quick video, which epitomizes the illusory weirdness of living one’s formative early years in front of millions of eyes.

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>>19110128

>why isn't woods standing w people like

https://futurism.com/pope-guide-artificial-intelligence

The Pope Just Released a Guide to Artificial Intelligence

The Pope Just Released a Guide to Artificial Intelligence

Sounds like that Pope Drip picture really got to him.

The Pope has released a guidebook on AI ethics. Yes, you heard that right.

The supreme pontiff has partnered with Santa Clara University's Markkula Center for Applied Ethics to form the Institute for Technology, Ethics, and Culture (ITEC), a body that, according to its website, is designed to convene "leaders from business, civil society, academia, government, and all faith and belief traditions, to promote deeper thought on technology's impact on humanity."

Think of it as a Vatican-led AI ethics think tank.

Its first order of business is releasing a handbook, called "Ethics in the Age of Disruptive Technologies: An Operational Roadmap," meant to help tech companies navigate the many grey areas of AI ethics.

"The Pope has always had a large view of the world and of humanity, and he believes that technology is a good thing," Father Brendan McGuire, a pastor and ITEC advisor, told Gizmodo. "But as we develop it, it comes time to ask the deeper questions."

"Technology executives from all over Silicon Valley have been coming to me for years and saying, 'You need to help us, there’s a lot of stuff on the horizon and we aren't ready,'" he added. "The idea was to use the Vatican's convening power to bring executives from the entire world together."

To be fair, the handbook doesn't just focus on AI and machine learning. It also covers other topics like encryption, tracking, and facial recognition technologies.

Still, based on the text, the ongoing AI race certainly seems to be its main inspiration.

"Since I have begun meeting and talking with senior representatives of Silicon Valley, especially those working in the area of artificial intelligence and machine learning, I have been impressed by their desire to maintain high ethical standards for themselves and for their industry," reads an opening chapter of the handbook, penned by the Irish Bishop Paul Tighe.

"This is already clear in the number of initiatives that seek to ensure that technology will be at the 'service of humanity,' 'for good,' 'human centered,' 'ethical by design,' and 'open,'" he added. "This desire to maintain ethical standards reflects both an intrinsic commitment to doing good and a realistic aversion to the risk of reputational damage and long-term commercial harm."

In other words: business leaders are knowingly using these buzzwords to win trust — and make a buck. But how, exactly, do companies actually follow through with those human-centered and "don't be evil" promises? And besides, what does this all have to do with the Pope anyway?

Make no mistake — elsewhere in his chapter, Tighe described the handbook as the "fruit of an unlikely cooperation," and the Catholic Church seems well aware of the fact that their archaic, old-world institution and Silicon Valley couldn't be more different from each other.

That said, the existence of the ITEC could be seen as a sign of AI's real and potentially transformational staying power. After all, His Holiness never published a 140-page guidebook on crypto.

It's also worth noting that the ITEC isn't pretending that its handbook is an effective replacement for government regulation. While we wait for regulators to jump into action — something that could take quite some time — the Institute says that their guidelines can help burgeoning companies keep consumer health and ethics front and center.

That is if they feel inclined to do so.

"Major guardrails are absolutely necessary, and countries and governments will implement them in time," Brendan, who reportedly does not know whether the Pope has used ChatGPT, told Gizmodo. "But this book plays a significant role in fast tracking the approach to design and consumer implementation."

"That's where we're trying to enable companies to meet the standards we need way ahead of time," he added.