Do mRNA COVID-19 (Coronavirus Disease 2019) vaccines continue to produce spike protein in human cells long after injection?

Scientific Evidence for mRNA Vaccine Spike Protein Production Duration

There is limited scientific evidence supporting the claim that mRNA COVID-19 vaccines continue to produce spike protein in human cells long after injection, with most research indicating spike protein production is temporary and limited to days or weeks.

Mechanism of mRNA Vaccines and Spike Protein Production

How mRNA Vaccines Work

• mRNA vaccines deliver modified messenger RNA encoding the SARS-CoV-2 spike glycoprotein to host cells 1
• After intramuscular injection, the mRNA enters cells and uses cellular machinery to produce spike protein
• The spike protein then triggers an immune response, generating antibodies and cellular immunity

Expected Duration of Spike Protein Production

• Original estimates suggested that injected mRNA would degrade within a few days 2
• The spike protein was initially expected to persist for only a few weeks 2
• BLI (bioluminescence imaging) studies in mice showed protein production peaked early and declined over time 1

Current Evidence on Duration of Spike Protein Production

Clinical Studies on mRNA Persistence

• Recent studies indicate modified SARS-CoV-2 mRNA can persist up to a month after injection 2
• The Pfizer/BioNTech COVID-19 vaccine was evaluated using in vivo bioluminescence imaging at six time points (6h, 24h, 48h, 72h, 6d, 9d post-injection) in mice 1
• These longitudinal measurements were performed in only 6 anesthetized mice, limiting the strength of evidence 1

Spike Protein Detection in Tissues

• Some research suggests spike protein may be detected in cardiac and skeletal muscle at sites of inflammation 2
• Recombinant spike protein has been reported to persist "a little over half a year" in blood according to some studies 2
• A mass spectrometry method has been developed to detect and quantify spike protein expressed after transfection with mRNA vaccines 3

Potential Mechanisms for Extended Production

mRNA Modifications

• COVID-19 vaccines contain nucleoside-modified messenger RNA (mRNA) 2
• 1-methylpseudouridine enrichment may affect mRNA stability and translation 2
• These modifications could potentially affect breakdown, transcription, and protein synthesis 2

Frameshifted Proteins

• Some research suggests vaccination with modified mRNA can produce peptides derived from +1 ribosomal frameshifting 2
• These products might impact host T cell immunity and B cell antigen production 2

Clinical Implications and Safety Considerations

Myocarditis Risk vs. Benefit

• Rare cases of myocarditis have been reported following mRNA vaccination, particularly in young males 1, 4
• For every 1 million males aged 12-29 years receiving a second dose, there is a risk of 39-47 cases of myocarditis 1, 4
• However, this same vaccination prevents 560 hospitalizations, 138 ICU admissions, and 6 deaths 1, 4
• The benefit-to-risk ratio strongly favors vaccination across all age and sex groups 1

Hypothesized Mechanisms of Adverse Effects

• Some researchers hypothesize that spike protein itself may have proinflammatory effects 5, 6
• There are reports suggesting spike protein might affect endothelial cells 6
• However, these findings are primarily from cell-based assays or animal models 5

Limitations of Current Evidence

Research Gaps

• Most studies on spike protein persistence are limited in sample size and duration
• The clinical significance of detected spike protein fragments remains unclear
• The most recent research claiming long-term persistence 2 lacks peer validation and contradicts earlier studies

Methodological Considerations

• Detection methods vary significantly between studies
• Some studies may detect spike protein fragments rather than intact functional protein
• The relationship between detectable protein and biological activity is not well established

Conclusion

While some recent research suggests mRNA and spike protein may persist longer than initially expected, the highest quality evidence indicates that mRNA vaccines produce spike protein transiently, with production declining significantly within days to weeks. Claims of long-term spike protein production (beyond a few months) lack robust scientific support from large, well-designed studies. The benefit-risk assessment of COVID-19 mRNA vaccines remains strongly favorable across all populations studied.