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The development of mutations in virus is reported to happen during replication, especially for an mRNA type virus like SARS-COV-2

Viruses that encode their genome in RNA, such as SARS-CoV-2, HIV and influenza, tend to pick up mutations quickly as they are copied inside their hosts, because enzymes that copy RNA are prone to making errors

My question is do mutations occur while mass manufacturing inactivated viral vaccines?

Simply because the process of manufacturing inactivated vaccines replicate the virus in large quantities, there might be large number of mutations occurring. Will this make each batch different from one another? Or do they control the replication process to limit the mutations?

Veritaisum did a recent video on the study on mutations in long term evolution experiment of E.Coli. It is clear that mutations do occur even in standard controlled environment.

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  • $\begingroup$ I already asked in medical sciences stackexchage medicalsciences.stackexchange.com/q/27469/22302. Reposting here for visibility $\endgroup$
    – karthikeyan
    Jun 21 '21 at 6:30
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    $\begingroup$ "inactivated viral vaccines" - note that the major Covid vaccines are not of this type. Moderna and Pfizer are mRNA vaccines. Astra-Zeneca and Janssen uses harmless non-Corona viruses. $\endgroup$
    – MSalters
    Jun 21 '21 at 15:56
  • $\begingroup$ Please don't repost questions. For this one, this site is more appropriate than Medical Sciences. $\endgroup$
    – MattDMo
    Jun 21 '21 at 16:14
  • $\begingroup$ @MSalters there is a significant portion of covid vaccines manufactured using inactivated viruses. And mRNA vaccine is not a viable in many parts of the world. Hence asked this question $\endgroup$
    – karthikeyan
    Jun 24 '21 at 15:06
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    $\begingroup$ @karthikeyan I'm sure there was no harm intended, but it's against the Stack Exchange rules. If you didn't get a result elsewhere after a few days, just delete the question and then repost it here. We just don't want multiple parallel discussions going on at different sites. $\endgroup$
    – MattDMo
    Jun 24 '21 at 16:13
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Very simply, mutations do occur, as they do for any cultured organism. This is a well recognized problem in many fields of biology where organisms are cultured and remains in particular a problem for cultured mammalian cell research.

As far as I know there is no method for slowing or altering the rate of mutation as this is an inherent part of the RNA-dependent RNA polymerase. This happens irrespective of the environment the virus is grown in and is one of the ways that viruses of this sort combat the immune system and ecosystem changes - they produce so many mutations over the generations of viral replication that some of the progeny will be more fit in the environment in which they are replicating.

In fact, they produce so many mutations at each replication cycle that these viruses can not be called a single "species" they are actually what is referred to as a quasispecies.

It is part of the difficulty of producing vaccines against things like influenza and related viruses as they can change from the phenotype seen in the wild. However, we have methods of checking that the viruses are the same or similar enough antigenically that it makes no difference for the immune response to the vaccine.

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    $\begingroup$ IIRC, you can change the rate of mutation by changing codons. There are 64 codons for 20 amino acids, so not all mutations will change the resulting virus. For example, "CUA" and "UUA" both encode for Leukin, but "CUA" is more stable. That's because an A->U mutation would produce "CUU" and "UUU", but only CUU encodes for Leukin. $\endgroup$
    – MSalters
    Jun 21 '21 at 16:02
  • $\begingroup$ @MSalters - yes, this potentially outputs stable functional viruses, however in a normal infection (in the lab) defective particles outweigh the functional by some orders of magnitude. The error rate of the RdRP is constant for the virus, so even if you have the CUA codon, it doesn't mean it will change the rate at which it is mutated, just that functional virions will more likely have this codon. $\endgroup$
    – bob1
    Jun 21 '21 at 22:26
  • $\begingroup$ @bob1 I haven't looked at this in years, but I believe the codon can actually affect the mutation rate and certain codons are more prone to slippage and are more likely to be read by the wrong tRNA than others. Take this with a huge grain of salt, I am vaguely remembering conversations with colleagues from several years ago, but I do think there is something along those lines. $\endgroup$
    – terdon
    Jun 22 '21 at 14:42
  • $\begingroup$ @terdon - in what systems? We are talking about an RdRP in viruses here. $\endgroup$
    – bob1
    Jun 22 '21 at 20:30
  • $\begingroup$ @bob1 huh, good point. If (big if) my memory serves me and there are indeed different rates of error for different codons, I would expect that to also be the case for viral RdRP. But I'm really just making wild guesses and assumptions based on vague recollections so I certainly won't press the point. $\endgroup$
    – terdon
    Jun 22 '21 at 21:51

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