Self-replicating/self-amplifying RNA “vaccines” are disasters on steroids

Despite being promoted as resolving 1st generation mRNA issues, they amplify existing problems and lack any proof or rationale for increased safety

The new hype surrounding self-replicating/self-amplifying RNA technology has escalated. Recently, within one day, the announcements of two purportedly successful trial results have flooded the media.

The first news concerns research done by Replicate Bioscience which proudly announced that “Replicate’s srRNA Rabies Vaccine Effective in Phase 1.” The second praises the Phase 3 trial results by CSL/Arcturus Therapeutics (ARCT), emphasizing “New COVID-19 sa-mRNA Results from CSL and Arcturus Therapeutics Demonstrate Longer Duration of Immunity Compared to Conventional COVID-19 mRNA Vaccine Booster.”

Known and emerging dangerous aspects of mRNA vaccines are ignored and instead portrayed as beneficial. The new platforms clearly amplify existing problems and may also engender new risks.

The essence of self-replicating/self-amplifying RNA technology 

These RNA platforms were already studied before the pandemic, with serious limitations known already years ago. In my book, I discussed these in detail.

• The goal of these technologies has always been to obtain greater quantities of antigen made from a smaller amount of vaccine.

• In essence, this is realized via an in vivo self-amplifying mRNA construct. This means that in addition to the RNA encoding the targeted protein, the genetic injections also encode replicase components able to direct intracellular mRNA amplification.

• Again, please note the sole goal of the entertainment - to express high levels of the antigen of interest as long as possible.

What is promised

Bioscience, in particular, describes the need for self-replicating (srRNA) technology and the promised benefits as follows:

“Replicate Bioscience, an Apple Tree Partners portfolio company, is a clinical-stage company amplifying the power of RNA therapeutics by pioneering its novel self-replicating RNA (srRNA) technology to overcome the shortcomings of existing mRNA approaches, with potential improvements in bioactivity at lower doses, induction of more robust and durable immune responses, and improved tolerability.”

Likewise,  CSL/Arcturus Therapeutics, in their announcement of their ”follow-up analysis of a Phase 3 study evaluating a booster dose of ARCT-154, the world's first approved self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine,” highlighted the purported benefits:

“self-amplifying mRNA vaccines instruct the body to make more mRNA and protein to boost the immune response.”

and

“The new analysis at 6 months post-vaccination shows that ARCT-154 induces a longer immune response as compared to Comirnaty for both the original Wuhan strain and Omicron BA.4/5 variant and an advantage in antibody persistence.”

Indeed, ARCT-154 was administered at one-sixth the dose of Comirnaty® (5 μg vs 30 μg, respectively). But it isn’t only about the dose that gets injected.

Trial Flaws

This note is not about the trials per se. Yet, several shortcomings are immediately obvious:

• It is important to realize that neither of the trials were independent RCTs tested against a true placebo group.

a) In Bioscience’s case, all participants received one or two doses of the srRNA vaccine.

b) ARCT described their trial as a “randomized, double-blind, active-controlled study.” In active-control trials, an experimental treatment is compared with an established treatment. In their case, booster results of the new vaccine were compared to  Comirnaty®. Because they call it a booster, this also means that participants had previously received some injection(s).

• There is no independent information on patient pre-selection & retention, data processing, etc. The slogan that it was well-tolerated (“no severe adverse events”) is rather meaningless in such a context. (I devoted an entire chapter in my book on related issues involving the mRNA Covid-19 “vaccines”).

• What was evaluated was not genuine immunity leading to factual protection against infection. Rather, the hype all centers on a “surrogate metric of protection.”

As stated by Replicate Bioscience,

“At all assessed doses, RBI-4000 achieved a strong immune response with protective virus-neutralizing antibody titers above the World Health Organization (WHO)-defined immune surrogate level of protection against the rabies virus.”  

This has been a common trick in recent years. Almost all studies now equate “protection”  with neutralizing antibody titer levels. But this is a useless surrogate (more below).

Trial Results

On Feb. 5, 2024, ARCT announced Phase 3 results of boosting with their ARCT-154 self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine, compared to a “conventional” mRNA COVID-19 vaccine. 

Effect on Wuhan-Hu-1: 

1. At baseline, participants in both the ARCT-154 and the Comirnaty® arm had similar geometric mean titers (GMTs) surrogate virus neutralizing antibodies against Wuhan-Hu-1 strain  (GMT ratio was 0.94 (95% CI 0.78-1.13)).

2. One-month post-booster (p.b.), the ARCT-154 group displayed a higher immune response with GMT of 5390 (95% CI 4899-5931, n = 378) compared to the Comirnaty® group with GMT of 3738 (95% CI 3442-4060, n = 367).

3. Three months p.b., GMTs were 5928 (95% CI 5414–6491, n = 369) and 2899 (2648–3175, n = 356). Notably, Day 91 titers were equal to or greater than Day 29 titers in 205 of 369 (55•6% [95% CI 50•3–60•7]) ARCT-154 recipients, but in only 108 of 356 (30•3% [25•6–35•4]) Comirnaty® recipients.

4. By Day 181 GMTs were 4119 (95% CI 3723–4557, n = 332) and 1861 (1667–2078, n= 313) in ARCT-154 and Comirnaty® groups, respectively. GMTs against Wuhan-Hu-1 remained numerically higher 180 days after ARCT-154 than those observed 28 days after the Comirnaty® booster.

This striking finding of the high and prolonged antibody titers is summarized below.

What seems particularly worrisome is:

• For the self-amplifying vaccines, titers increased even after 1 month still, apparently peaking around 3 months post booster (to put this into perspective: with 1^st generation mRNA vaccines, the highest titer was mostly observed around 28 days post-booster).

• Even half a year post booster, titers for the new platform were still higher than 28 days after the booster with the original vaccine.

• (By contrast, adaptive immunity hinges on immune memory, and the antibody decline is an inherent safety response that aims to restore homeostasis - rather than the ongoing arousal of an immune response.)

The finding of such insanely high antibody levels 6 months post-poster  is shocking.

As for Omicron, ARCT asserts the following:

“The same pattern of superior immunogenicity and slower decline in Omicron BA.4/5 neutralizing antibodies was observed.”

For details, please see here, summarized in the figure below. Ironically, these data strongly suggest that even the key goal of self-amplifying vaccines cannot be realized in the context of a rapidly mutating virus.

Despite all the push to increase antibody titer, the above effectively demonstrates that this goes against basic natural principles:

• The much lower titer (compared to the Wuhan strain) suggests the presence of several mechanisms that work against the design criteria of self-replicating/self-amplifying platforms.

• These technologies cannot mitigate effects such as immune imprinting (where the actual immune response induced by repeat exposures to antigenically distinct viral strains is influenced by previous exposures, and in the context of mRNA vaccines can be rather detrimental - I discussed much of this in my book).  

• As these technologies are also not designed to provide sterilizing immunity, and in fact, cannot, they do not resolve viral immune evasion, vaccine mismatch & further viral escape (again, for more, please see my book).

The design agendas and goals heavily contradict established knowledge

What is particularly troubling is that pharma companies admit the existence of shortcomings of current mRNA approaches. Indeed, this is why, they argue, new platforms are urgently needed.

While numerous errors and pitfalls of existing mRNA technologies are known, some of the most basic ones are the following (I have described all these in greater detail in my book):

• Broad dissemination of the injected material (as is well established now, it does not just “stay in the arm”).

• No clear dose-response relationship between what is injected and the evoked biological effect: the reasons for this are plenty-fold, ranging from numerous manufacturing issues to the unique immunological and pathophysiological environment of the vaccinees.

• Persistence of the injected material (again, there is a host of unique factors that influence the degree to which, if at all, the synthetic material  is being degraded; as is well-established by now, the reality of the poor degradability of the specially stabilized mRNA, further “protected” by the lipid nanoparticles, is terrifying).

• What should be clear now is that coercing human cells to produce foreign proteins (e.g. the spike) is not a good idea. Even if it’s done in a limited manner, the immune response to such toxins can be highly destructive, triggering a cascade of adverse effects.

• The immune response triggered by mRNA vaccines is difficult to predict: the actual outcome is again very individualized; yet, if there is any common pattern, it encompasses a corruption and misdirection of both arms of the immune system (e.g. excessive and destructive immune responses, autoimmune reactions, tolerance development, and immune priming).

• The idea that systemic immunization should be able to drive mucosal immunity (as would be needed for respiratory pathogens such as SARS-CoV-2).

• mRNA injections are not sterilizing, fostering viral escape and leading to an ongoing vaccine mismatch.

Neither of the above is mitigated by self-amplifying RNA vaccines. By contrast, the very agenda to extend and amplify antigen expression and additionally to induce a stronger and greater immune response is more than just a doubling down of grave errors of the existing mRNA vaccines.

Safety is being ignored

In neither of the above trial results, there is any clear indicator that safety was a key driver. If so, then the above, and related safety issues with mRNA vaccines would have been acknowledged and the entire entertainment would have been stopped in its very tracks.

With the new platforms, the injected material will also go everywhere, be resistant to normal degradation, trigger a host of unwanted/adverse effects, and all the while without any proof that it is safe or effective.

The safety of gene-technologies cannot be demonstrated via a small number of healthy participants, in a study that lacks clear public scrutiny, and which is done within a few weeks or months only. There are numerous reasons why previously the FDA insisted that these types of therapies be tested for several years, as indeed delayed long-term effects may only be seen after 10-12 years, or in the next generations (for more, please see my book).

Amplifying existing problems

By their very design, srRNA/saRNA technology is expected to amplify some of the known problems of first-generation mRNA vaccines (for more details, please see my book).

Unwanted/detrimental RNAs:

It has long been known that synthetically generated RNA is not always the nice, single-stranded complete RNA string that is expected. Instead, one may find:

• dsRNAs - directly from the in-vitro manufacturing process, but also generated in vivo. In my book, I devoted a lot of attention to dsRNAs. Long before the pandemic, their detrimental role as unwanted byproducts of mRNA vaccines was well established. This includes excessive immune responses but also their potential to negatively impact immune memory. Additionally, I described why dsRNAs originating from the vaccines have substantial mutagenic potentials and I outlined various mechanisms of how they could result in the genetic modification of human cells or those of the human microbiome.

• Fragmented mRNA molecules - which would therefore not encode the target protein (e.g. the spike) or which could result in undesirable off-target products. Depending on the manufacturing process used, it may also be possible to get RNA/DNA hybrids and other aberrant RNA species.

• The potentially highly deleterious aspects of vaccine-derived RNAs acting as regulatory RNAs have been largely underappreciated.  

These issues may be further enhanced by the sa/sr RNA platforms:

• For example, Bioscience claims the superiority of its technology over linear mRNA. Recently, circular mRNA and others have triggered enormous attention, promising the benefit that the ribosome will just keep making more protein and not fall off; in reality, the fidelity of protein production may be highly disturbed. There is no reason to believe that the ribosome will smoothly progress these synthetic mRNAs as planned. More likely than not, as is already known for pseudouridine, the various modifications done to the mRNA will result in unintended characteristics (e.g. folding, ribosomal loading, effects on translation) and aberrant proteins.

mRNA expression:

• The basic principle of the new technologies is still the same, albeit largely increased: cell gets hijacked to act as a toxin-producing factory to generate the largest amount of toxins.

• Several mechanisms have been envisioned (again, please see my book for details) as to why even with the 1^st generation mRNA vaccines there can be an ongoing expression of the synthetic mRNA (this can involve the possibility that the mRNA is taken up into the nucleus or by the human microbiota, combined with the observation that the synthetic material is not degraded). These issues are not mitigated by srRNAs/saRNAs.

• By contrast, for sRNAs/saRNAs, there is much less potential for a clear off-switch: Although Bioscience, for example, promises that its platform guarantees “controlled and self-limiting amplification” of the mRNA, this just too well reminds us of the previous promise of “controlled and time-limited” expression of the mRNA during the existing mRNA vaccines.  

The type of protein produced:

The mRNA in the existing mRNA vaccines has been synthetically modified for stabilization and immunity purposes. Ironically, while some still celebrate the Nobel prize invention of replacing ‘uridine’ with ‘N1-methyl pseudouridine,’ human ribosomes have some issues with Pfizer’s vaccine. As clearly demonstrated, the synthetic modification results in ribosomal frameshifting’ about 8% of the time which causes cells to produce off-target proteins which may be highly deleterious. It is clear this is not a new problem:

• Different pharma companies and researchers have long been pursuing alternative ways to modify the  mRNA. As seen from the methyl pseudouridine debacle, the issue is still insufficiently understood. However, sa/srRNAs platforms even increase the need for mRNA modifications (i.e., to enhance stability or to prevent the immune system from attacking and destroying the product itself).

• Additionally, sa/srRNAs likely employ additional codon optimization tricks to further enhance antigen production. This will likely result in additional off-target proteins and increased toxicity (e.g. harmful proteins or pathogenic prions).

• Many of the optimization strategies and synthetic modifications are proprietary information and not open to public scrutiny & debate.

Increased potential for adverse events

As mentioned, CSL & Arcturus Therapeutics claim that more mRNA and antigen will boost the immune response. This narrative is highly flawed, as has been known for years already (please see my book for details).

• The elevated and continued presence of the same antigen may actually down-regulate any protective immune responses (i.e. T-cell exhaustion or tolerance).

• Alternatively, more mRNA and antigen can lead to excessive immune reactions or autoimmunity.

• Their elevated/prolonged presence will likely enhance their toxic effects for (a) the vaccinees themselves, (b) those in close contact (aka, shedding), (c) their offspring.  

One of our worst fears with mRNA vaccines has recently been confirmed. Vaccinated women not only transmit the antigens to their offspring - as was already observed with self-amplifying mRNA (SAM) vaccines encoding bacterial antigens in murine models in 2017 (discussed in my book).

Sadly, it is now confirmed that babies are getting both Covid-19 vaccine mRNA and spike protein through the blood supply from the placenta. Even though the most pressing questions regarding quantity, immune reactions, and the full impact on development and future adverse events are unknown, it is clear that amplification of these toxins, as done via sa/srRNAs is not a good idea.

Antibody levels are NOT a proxy of protection

Already in January 2022, a Nature article pointed out that in the context of “coronavirus immunity, antibodies have stolen the limelight,” exposing “how fragile antibody-based immunity can be in the face of a changing virus.”

In my book, I spent an entire chapter on this and related issues, highlighting why antibody levels are no useful proxy of protection at all. For example:

• Already in 2021, Pfizer admitted the importance of T cell immunity.

• Serum antibody titers often correlate with disease severity: patients with severe Covid-19 disease may have a higher number of anti-SARS-CoV-2 serum antibodies than patients who recover quickly.  

• Systemic Versus Mucosal Immunity: Plasma IgG levels are not a measure of mucosal immunity - which would be essential for respiratory viruses such as SARS-CoV-2.

• The overlap between systemic and mucosal immunity shows that the narrative is foundationally flawed: elevated and prolonged antigen presentation may lead to tolerance development, T cell exhaustion, and IgG class-switching, with the net effect of declining and even negative protection.

• Declining and negative protection were first seen in some studies from Israel in 2022 following the 4^th dose of mRNA vaccines - the negative effects took place despite a huge increase in IgG and neutralization titers following the booster.

• Already on May 19, 2021, the FDA, the FDA advised against the use of SARS-CoV-2 antibodies as a surrogate for immune protection, stating

“results from currently authorized SARS-CoV-2 antibody tests should not be used to evaluate a person’s level of immunity or protection from COVID-19 at any time, and especially after the person received a COVID-19 vaccination.”

• NAb titer cannot be equated with immune protection; rather than being a suitable proxy of protection, it gives a false sense of immunity and furthermore cannot account for concerns such as immune imprinting and viral escape driving resistance.

Conclusion

Sa/srRNA platforms do not address any single known problem of first-generation mRNA technologies (for additional references, not explicitly stated above, please see my book). They do the opposite:

1. Whereas previously their precursors were, according to some legislations, “gene-therapy processes” (see my book), the new platforms are genetic injections on steroids.

2. They are designed to amplify some of the most concerning problems. They are built to increase and maintain the most toxic components.

3. What is described as superior immunogenicity solely relies on faulty measures - neutralizing antibody titers are not an adequate proxy for protection. While this was even emphasized by the FDA in 2021, the narrative has meanwhile changed, enforcing this flawed narrative of a useless and misleading proxy.

4. These platforms do not even intend to be able to prevent infection or to provide sterilizing immunity.

5. It is not about the dose that gets injected. mRNA technologies resemble active pharmaceuticals. What matters is how the body copes with these drugs and not, how cost-effective it is (manufacturers need lower doses).

6. All the knowns and unknowns about these technologies are concerning. We do not have large and unbiased studies with long-term follow-up. Additionally, many details are proprietary and not published.

7. We do not know technical details about manufacturing itself, meaning that we have no clarity about contamination issues, especially when produced at scale.

8. The fact that companies steer away even from linear RNAs is concerning as circular and other RNAs are known to result in aberrant and unwanted constructs.

9. We also lack clear and unbiased information about the viral components used during manufacturing to provide the enzymes that facilitate the amplification of the mRNA. Many questions have not been addressed, such as their on- and off-target activities, their persistence and degradation in the body, and manufacturing issues.

10. It has been known for years that dsRNA byproducts, in particular, cause a whole host of problems for mRNA technologies. IMHO, this topic is largely under-appreciated. In my book, I devoted large sections to their grave concerns. It has long been known that these will be exaggerated with self-replicating/self-amplifying technologies.

11. Some of the greatest dangers of dsRNAs and other aberrant species associated with mRNA technologies is their high mutagenic potential: several mechanisms are now known of how they can get into the nucleus and even (retro)integrated into the genome of humans or their microbiota.

12. The “optimization” strategy of sr/sa RNA technologies will inherently exaggerate their shedding potential - which initially had even been acknowledged by Pfizer during their trials for their 1^st gen vaccines.  

13. It is impossible to believe that the synthetic RNAs or the generated products cannot impair the human microbiome.

14. Environmental risks, e.g. via various unintended interactions between the genetic injections and other life forms or during their disposal, are likewise expected to intensify.

15. Some of the worst dangers of the enhanced/prolonged presence of the vaccine products are, in addition to their direct impact on immunogenicity and development in the offspring of vaccinated women, their risk for genetically adulterating those babies.