We comment on the study by Mulroney et al.(1) entitled: “N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting.” (https://www.nature.com/articles/s41586-023-06800-3) The study found evidence in mice and humans for the misreading of the modRNA contained within the Pfizer COVID-19 vaccine to inadvertently produce “off-target” proteins capable of eliciting “off-target” immune responses. The authors propose that these novel proteins are the result of ribosomal frameshifting occasioned by the substitution of N1-methyl pseudouridine. The authors state that the “error prone” code is a safety concern with a “huge potential to be harmful” and that “it is essential that these therapeutics are designed to be free from unintended side-effects.” The findings reveal a developmental and regulatory failure to ask fundamental questions that could affect the safety and effectiveness of these products. According to WHO guidelines for mRNA vaccines, (2) manufacturers should provide details of “unexpected ORFs” (Open Reading Frames). The formation of these off-target proteins is not disclosed in the package insert for COMIRNATY. The finding that unintended proteins may be produced as a result of vaccination is sufficient cause for regulators to conduct full risk assessments of past or future harms that may have ensued. Given that this study was conducted under the auspices of the United Kingdom Government, we must assume UK regulators, manufacturers, and international regulatory agencies, including FDA, were apprised of the data many months ago. We await their account of what steps they have taken to investigate why the formation of off-target proteins was not discovered sooner, what toxic effects they may have caused and what steps they are taken to prevent harm in the future and to inform the public of these findings.
The authors state that “Although there is no evidence that frameshifted products in humans generated from BNT162b2
vaccination are associated with adverse outcomes.” It is unclear how it is possible to make this statement, given:
• The small number of vaccinated subjects (n=21) providing samples.
• This was not a controlled trial.
• None of these subjects had reported undue effects of vaccination. Accordingly, the sample is subject to selection
bias.
• The toxicology of these unintended proteins must be studied.
• The authors acknowledge the misdirected immunity “has huge potential to be harmful.”
• These proteins may already have contributed to vaccine toxicity, which now must be the subject of investigation.
The full sequence of these proteins should be provided. Further, the homologies between the proposed frameshifted
proteins and peptides and known proteins must be conducted using databases and tools such as BLAST. One of the
proteins identified was characterized as a chimeric protein. McKernan et al. (5) showed how in theory, a chimeric viral-
human protein might be formed that has a homology similarity to a human protein called gp130, which forms part of a
receptor for IL-6.
The premise for the study reveals a developmental and regulatory failure to ask fundamental questions that could affect
the safety and effectiveness of these products. This is no better exemplified by Pfizer’s retired head of vaccine R&D who
was quoted in Nature as saying: “We flew the aeroplane while we were still building it.” (6)
“The complete annotated sequence identifying all ORFs (including any unexpected ORFs) and all other sequence
elements (including their justification for use) should be provided. Justifications for the use of any specific noncoding
sequence and of structural elements such as the chosen 5` cap structure should be provided. [..] The anticipated function
and purpose of each gene sequence encoded in the mRNA should be indicated, as well as those of specific noncoding and
structural elements, explaining their contribution to the overall mode- or mechanism-of-action.”
If Mulroney et al. were able to predict the existence of frameshifted proteins, why were Pfizer’s scientists unable to do so?
The same question may be asked of regulators, especially in light of unresolved discrepancies and the specific obligation
imposed by the European Medical Agency on BioNTech regarding the identities of the observed Western Blot (WB) bands
obtained by in vitro expression assays.(7)
Documents disclosed under the FOIA (8) reveal that three categories of preclinical studies were not performed by Pfizer,
relevant to the current findings: 1) secondary pharmacodynamics, 2) safety pharmacology and 3) pharmacodynamic drug
interactions, In two of these categories, WHO guidelines were cited in justification (highlight added).
The package insert for COMIRNATY states (3):
“Each 0.3 mL dose of COMIRNATY (2023-2024 Formula) is formulated to contain 30 mcg of a nucleoside modified
messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Omicron variant lineage XBB.1.5
(Omicron XBB.1.5).”
There is no mention of any other kind of protein.
The finding that unintended proteins may be produced as a result of vaccination is sufficient cause for regulators to conduct
full risk assessments of past or future harms that may have ensued. We note that regulators have previously failed to insist
on the study and assessment of risk of the pharmacology and toxicology of novel spike protein heterotrimers forming after
injection of the bivalent COVID-19 modRNA vaccines.(9)
The authors state that “Although there is no evidence that frameshifted products in humans generated from BNT162b2
vaccination are associated with adverse outcomes.” It is unclear how it is possible to make this statement, given:
• The small number of vaccinated subjects (n=21) providing samples.
• This was not a controlled trial.
• None of these subjects had reported undue effects of vaccination. Accordingly, the sample is subject to selection
bias.
• The toxicology of these unintended proteins must be studied.
• The authors acknowledge the misdirected immunity “has huge potential to be harmful.”
• These proteins may already have contributed to vaccine toxicity, which now must be the subject of investigation.
The full sequence of these proteins should be provided. Further, the homologies between the proposed frameshifted
proteins and peptides and known proteins must be conducted using databases and tools such as BLAST. One of the
proteins identified was characterized as a chimeric protein. McKernan et al. (5) showed how in theory, a chimeric viral-
human protein might be formed that has a homology similarity to a human protein called gp130, which forms part of a
receptor for IL-6.
The premise for the study reveals a developmental and regulatory failure to ask fundamental questions that could affect
the safety and effectiveness of these products. This is no better exemplified by Pfizer’s retired head of vaccine R&D who
was quoted in Nature as saying: “We flew the aeroplane while we were still building it.” (6)
“The complete annotated sequence identifying all ORFs (including any unexpected ORFs) and all other sequence
elements (including their justification for use) should be provided. Justifications for the use of any specific noncoding
sequence and of structural elements such as the chosen 5` cap structure should be provided. [..] The anticipated function
and purpose of each gene sequence encoded in the mRNA should be indicated, as well as those of specific noncoding and
structural elements, explaining their contribution to the overall mode- or mechanism-of-action.”
If Mulroney et al. were able to predict the existence of frameshifted proteins, why were Pfizer’s scientists unable to do so?
The same question may be asked of regulators, especially in light of unresolved discrepancies and the specific obligation
imposed by the European Medical Agency on BioNTech regarding the identities of the observed Western Blot (WB) bands
obtained by in vitro expression assays.(7)
Documents disclosed under the FOIA (8) reveal that three categories of preclinical studies were not performed by Pfizer,
relevant to the current findings: 1) secondary pharmacodynamics, 2) safety pharmacology and 3) pharmacodynamic drug
interactions, In two of these categories, WHO guidelines were cited in justification (highlight added).
The package insert for COMIRNATY states (3):
“Each 0.3 mL dose of COMIRNATY (2023-2024 Formula) is formulated to contain 30 mcg of a nucleoside modified
messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Omicron variant lineage XBB.1.5
(Omicron XBB.1.5).”
There is no mention of any other kind of protein.
The finding that unintended proteins may be produced as a result of vaccination is sufficient cause for regulators to conduct
full risk assessments of past or future harms that may have ensued. We note that regulators have previously failed to insist
on the study and assessment of risk of the pharmacology and toxicology of novel spike protein heterotrimers forming after
injection of the bivalent COVID-19 modRNA vaccines.(9)
