2. Modifications in the Vaccine mRNA Sequence
The technology behind the mRNA vaccines is complex and sophisticated,
and much about it is new and poorly evaluated for safety [14]. The
mRNA in the vaccines is very different from the mRNA sequence that the
virus uses to encode the spike protein. A significant modification was
to replace all of the uridines in the sequence with
methylpseudouridines. This allows the mRNA to resist enzymatic
breakdown. It has been shown that methylpseudouridine modifications
support more than ten times as much protein as unmodified mRNAs, in part
by preventing repression of translation initiation [15,16].
Other ingredients include polyethylene glycol and a synthetic cationic
lipid, which facilitates escape from the lysosome into the cytoplasm and
initiation of protein synthesis. The actual sequence itself is also
modified, through a process called “codon optimization,” which
involves substituting redundant codons that translate more efficiently
than the codons the virus used for each amino acid. A codon replacement
that actually changes the peptide sequence is also introduced, replacing
two adjacent amino acids with a double proline sequence that disrupts
the refolding step to facilitate membrane entry following binding to the
ACE2 receptor. Finally, the mRNA molecule is “humanized” by inserting
5’ and 3’ untranslated regions (UTRs) ) on its two ends, sequences
borrowed from long-lasting human mRNAs, and adding a long poly-A tail to
further promote resistance to breakdown [14]. The spike protein
shares regions of high molecular similarity with many important human
proteins, and molecular mimicry may lead to autoimmune disease,
especially because the vaccine induces a very strong antibody response
[17].
It appears that the developers were very successful in assuring rapid
synthesis of the spike protein sustained over a long period of time.
Most mRNA molecules are eliminated within a few hours of their
synthesis, whereas spike protein mRNA has been found in the draining
lymph nodes of the arm muscle two months after vaccination, and this
durability was associated with post-vaccine symptoms similar to the
symptomatic profile of long COVID [18]. Fertig et al. have
found mRNA circulating for at least two weeks after vaccination
[19].