Hi Kevin,

Have you seen any deep-sequencing reads that indicate there has been recombination between the vaccinal sequences and the various SarsCov2 variants?

It looks like the codon optimised “pseudo-mRNA” vaccines match the Wuhan spike at around ~85% at the nucleotide level, with plenty of 30+ exact identity regions throughout the spike ORF to provide plentiful template switching possibilities, even for a +ve str RNA virus.

Various chimeras appear to have been found between delta and omicron after (presumably) a coinfection. And it even appears various entirely new viral species have been formed similarly, including possibly SARS Season 1.

Repeatedly transfecting millions of people who are potentially infected, with the reportedly far milder omicron variants, with billions of copies of modified nucleic acids that could recombine with any replicating virus to restore some (all?) of the linked mutations that made the original strain more virulent, seems like a risky plan to me.

As for a “bivalent” booster, containing the template for a recent but outcompeted omicron spike mixed up with the original Wuhan spike, being transfected into cells that may be replicating even more homologous omicron RNA, seems even more likely to promote recombination, and thereby provide an intermediate that could help restore the full Wuhan spike, than the original monovalent vaccine.

Is it known if the spike ORF’s in the bivalent shots were codon re-“optimised” differently to the original vaccinal spike to reduce the possibility of recombination with one another? I’m guessing not, seeing as the people who designed these seem to be oblivious to or in denial of a huge variety of plausible issues, as you have so comprehensively demonstrated.

Also, given the heavy codon changes in the vaccinal sequences, would the sequencing primers used for the transcriptome sequencing bind to the vaccinal regions if so? Or put another way, do we know if the routine deep sequencing has even looked for vaccinal recombinants? This amazing deep-sequencing was well after my time…

I would find it very ironic if some of the S gene amplimer “drop out”, that appears to still (bizarrely) be used as a diagnostic for certain variants, is actually coming about through vaccinal spike recombinants. Why continue to use a negative result as a diagnostic??

And lastly - sorry for all the questions in one post - is it known if the LFTs would give a positive signal for a vaccinal spike recombinant if it arose? If neither PCR nor LFT detects such a recombinant, then there would be a selective advantage to any such detection-evading variant that arose, and such cases might never even be sampled for the deep-sequencing needed to detect their presence.

P.S. Thanks for all the awesome posts (and to get even nerdier, particularly the deep dive into the modern usage of Type IIs REs, so much easier to say than hapaxoterministic restriction enzymes as I was taught to call them in the UK. I had some “fun” with them back in the day - took me right back to the early days of my molbio career.)