The Future of mRNA Vaccines

(Review, Open Access) Long-lasting, biochemically modified mRNA, and its frameshifted recombinant spike proteins in human tissues and circulation after COVID-19 vaccination

https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.1218

Abbreviations

²H-D deuterium

mRNA messenger RNA

Polθ polymerase theta

SARS-CoV severe acute respiratory syndrome caused by corona virus

WT natural wild-type

Guest post by James Lech https://www.linkedin.com/in/jameslech/

Why It Matters

This study challenges our understanding of how long COVID-19 vaccine components remain active in the body and their potential long-term effects. It highlights the need for more research into the biochemical and quantum mechanisms at play, ensuring we fully grasp the implications of these groundbreaking vaccines.

Dive into the full study to uncover the science behind these startling findings and what they mean for the future of mRNA vaccines.

The study titled “Long-lasting, biochemically modified mRNA, and its frameshifted recombinant spike proteins in human tissues and circulation after COVID-19 vaccination” by Boros et al. presents a detailed analysis of the persistence and impact of modified mRNA used in COVID-19 vaccines. 

Here are the key points and findings from the publication:

Objectives

1. Evaluate the Persistence of mRNA and Spike Protein:
   • Investigate how long the modified mRNA from COVID-19 vaccines remains in human tissues and circulation.
   • Assess the duration for which the recombinant spike protein persists in the body post-vaccination.
2. Examine Immunological and Cellular Responses:
   • Explore the cellular and immune responses elicited by the modified mRNA and its translated products.
   • Analyze the potential off-target effects and immune responses due to frameshifted translation products.
3. Investigate Potential Adverse Effects:
   • Discuss the implications of prolonged presence of spike proteins on organ function and overall health.
   • Highlight any clinical observations of adverse events related to the persistence of these proteins.

Key Findings

1. Persistence of mRNA and Spike Protein:
   • The modified mRNA can persist up to 30 days post-injection in tissues such as the heart and skeletal muscle.
   • Recombinant spike proteins have been detected in the blood for over 187 days after vaccination.
2. Immune and Cellular Responses:
   • The study found increased production of new B-cell antigens and T-cell responses due to +1 ribosomal frameshifting.
   • Identified nine peptides derived from the +1 frame translation of the mRNA, which could impact host T-cell immunity.
3. Adverse Effects:
   • Documented increased uptake of 18-flourodeoxyglucose in heart muscle, indicating inflammation and metabolic changes post-vaccination.
   • Noted potential risks for myocarditis and other cardiac complications linked to prolonged presence of spike proteins.
   • Raised concerns about the stability of deuterium (heavy hydrogen) in proline and hydroxyproline residues in spike proteins, potentially contributing to long-term pathogenicity.

Clinical and Biochemical Insights

• Biochemical Modifications: The mRNA vaccines incorporate pseudouridine and methylpseudouridine, enhancing stability and reducing immediate immunogenicity but potentially contributing to prolonged biological activity.
• Proteomic Analysis: Mass spectrometry identified both in-frame and frameshifted peptides, suggesting that mRNA modifications lead to diverse protein products with possible immune implications.
• Deutenomics: Highlighted the role of deuterium in stabilizing mRNA and spike proteins, affecting their breakdown and potentially leading to extended persistence in the body.

Expanding into the proton tunneling importance from the work of Dr. Judith Klinman’s expertise:

Proton Tunneling and Enzyme Catalysis

1. Enzyme Catalysis and mRNA Stability:

• Proton tunneling is a quantum mechanical phenomenon where protons can pass through energy barriers rather than going over them. This has profound implications for enzyme catalysis, particularly in reactions involving hydrogen transfers.
• In the context of mRNA vaccines, the stability of mRNA molecules and their subsequent translation into spike proteins could be influenced by enzymatic processes where proton tunneling plays a role. This stability could impact the persistence of these molecules in the body.

2. Hydrogen Bonding and Structural Stability:

• Dr. Klinman’s work emphasizes the importance of hydrogen bonding networks in enzyme active sites and their role in facilitating proton transfer.
• Modified mRNA and the resultant spike proteins might have altered hydrogen bonding patterns due to biochemical modifications such as pseudouridine incorporation. These changes could influence the overall stability and degradation pathways of these molecules, potentially contributing to their prolonged presence in tissues.

Quantum Effects in mRNA Degradation and Translation

1. Proton Tunneling in RNA Decay Mechanisms:

• RNA degradation involves various nucleases and ribozymes, where proton transfer is a critical step. Proton tunneling could affect the efficiency and rate of these reactions.
• The biochemical modifications in mRNA vaccines might alter the typical proton transfer pathways, thereby affecting the decay rates of these molecules. This could explain the observed persistence of mRNA up to 30 days post-injection.

2. Enzymatic Processes and Modified mRNA:

• Enzymes like RNA polymerases and ribosomes, involved in the synthesis and translation of mRNA, could exhibit altered catalytic properties in the presence of modified nucleotides.
• Proton tunneling could influence the fidelity and efficiency of these enzymatic processes, potentially leading to the production of frameshifted recombinant spike proteins. This frameshifting might result in the generation of unexpected peptide products, eliciting off-target immune responses.

Implications for Long-term Protein Persistence

1. Proton Tunneling and Protein Folding:

• The proper folding and stability of proteins, including recombinant spike proteins, are crucial for their function and degradation. Proton tunneling can impact the folding pathways and stability of these proteins.
• The introduction of proline residues in spike proteins, as highlighted in the study, could create sites for increased deuterium (heavy hydrogen) binding. These sites might exhibit unique proton tunneling properties, contributing to the long-term stability and resistance to degradation of these proteins.

2. Deuterium and Enzymatic Action:

• Deuterium has different tunneling properties compared to protium (the most common hydrogen isotope), which could affect enzymatic reactions involving spike protein degradation.
• The accumulation of unregulated deuterium in proline-rich regions of spike proteins can lead to reduced degradation by proteases, resulting in their prolonged presence in circulation. This aligns with the study’s findings of spike protein persistence for over half a year.

Ref 12: “To stabilize or not to stabilize RNA – that is still the question”

P olymerase theta (Polθ) provides critical insights into the stability and potential genetic integration of RNA templates, which are directly relevant to understanding the findings in the Boros et al. study on COVID-19 mRNA vaccines. The role of Polθ in reverse transcribing stable RNA and the impact of deuterium on RNA stability highlight important biochemical mechanisms that could explain the prolonged presence and potential adverse effects of vaccine-derived mRNA and spike proteins in human tissues.

Ref. Boros LG, Kyriakopoulos AM, Brogna C, Piscopo M, McCullough PA, Seneff S. Long-lasting, biochemically modified mRNA, and its frameshifted recombinant spike proteins in human tissues and circulation after COVID-19 vaccination. Pharmacol Res Perspect. 2024; 12:e1218. doi:10.1002/prp2.1218

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