What's important to note, though, is that the mutations are blind to their environment. The virus or bacteria doesn't see an antibiotic or antibody and say "I need to adjust this aspect." It's just constantly changing as it reproduces, and some of them may end up winning a battle that the original did not. And then they spread from there as would any strain.
From the purposes of the virus, an unvaccinated person in a poor country without access to vaccines isn't better or worse than one in the US who's simply refusing. It doesn't know. They're both opportunities for the virus to keep replication and so keep (randomly, blindly) mutating.
If the odds of reproducing in a way that escapes people's current antibodies, and making your way outside the host (because a mutation the immune system adapts to before it can be spread dies there) are 1 in ten billion, say... and you leave 7 billion people in the world unvaccinated... suddenly those odds aren't so great. (Numbers entirely fake here, but basically, less likely events become more likely as more time goes by, if you keep giving them opportunities to happen.)
A key advantage of a vaccine over an antibiotic is that it can potentially stops the problem before it starts whereas antibiotics are generally given if you already have a nasty infection. So the amount of virus that's exposed to the immune system in a vaccinated person will be lower, and throttled more quickly, giving less time for it to get lucky, IIRC. But nothing about that would magically necessarily stop a virus that's still spreading like wildfire in a large unvaccinated population from coincidentally developing new traits that help it out. The goal is to vaccinate a large enough population quickly enough that this "spreading like wildfire" situation stops, so we reduce the mutation rate of the virus.
So as long as mutations like the epsilon variant don’t occur (they do right?) and as long as vaccines are prophylactic against infection (not the case given need for boosters is Israel, right?), there’s nothing to worry about? Sorry if I’m being dense.
[1] Why does drug resistance readily evolve but vaccine resistance does not? https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016...
[2] The adaptive evolution of virulence: a review of theoretical predictions and empirical tests https://www.cambridge.org/core/services/aop-cambridge-core/c...
“reducing the risk of death for infected hosts reduces the cost of virulence, causing an evolutionary increase in virulence (Gandon et al. 2003, 2001b). Vaccines that either block infection or block transmission, on the other hand, have no effect on virulence evolution”
Especially considering Dr Fauci’s recent statements on how the COVID vaccines do not block transmission.
https://m.youtube.com/watch?v=AuO_OfjlPUI
Putting these together then it seems like we should expect the result of our vaccination efforts to be increased virulence in strains such as Delta variant. Is it possible the Delta variant itself was somehow the result of our intrepid and swift vaccination efforts? I’m having a hard time understanding why more people aren’t talking about this given the obviously well established scientific literature you’ve cited.
> Is it possible the Delta variant itself was somehow the result of our intrepid and swift vaccination efforts?
The variants can arise under neutral genetic drift, ie pure random chance via naturally occurring mutation.
But the widespread dominance of these variants is very plausibly connected to the mass vaccination efforts.
Here is another good paper on the subject, in case you haven't already seen it [1].
> I’m having a hard time understanding why more people aren’t talking about this
Me too, but to be fair these are complex second and third order effects that only gained traction in the scientific literature within the past decade or so. Right now everyone is mostly focused on first order effects - eg "will the vaccination help/harm me?"
Quotes from [1]:
- "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection."
- "Our work suggests that it is likely that standing genetic variation alone has already produced a substantial population of viruses with single and double nucleotide changes that confer nAb resistance. These variants will establish quickly in the population under selection pressure. In fact, there is already a precedent for this behavior, as one such selective sweep occurred early on in the SARS-CoV-2 pandemic when the D614G mutation rose to nearly 80% frequency in under 6 months [33]."
[1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/
“one possible solution to the problem of immune evasion by SARS-CoV-2 that has been proposed is to develop a new vaccine update every year, similar to influenza [42]. In practice, such a solution will only work in the face of a moderate pace of evolution of SARS-CoV-2 and a low degree of clonal diversity among various clades of SARS-CoV-2 as they evolve to evade the current crop of vaccines. Further, if within-host evolution of SARS-CoV-2 contributes to population-level immune evasion, the valley-crossing mechanism described in this paper could accelerate the emergence of vaccine-resistant strains in the months following vaccine deployment. To the extent that new strains of SARS-CoV-2 are antigenically distinct, this may also lead to increased risk of antibody-dependent enhancement (ADE), as one mechanism for ADE involves antibodies that bind to the pathogen but fail to neutralize it [43]. Finally, our work suggests that immune evasion requiring one to two mutations occurs within months, raising the prospect that this phenomenon will further shorten the duration of natural immunity, which is already limited by the relatively short duration of the humoral [44,45] and cellular [46] responses to SARS-CoV-2 infection. Further studies are required to understand the risk immune evasion poses to a strategy of annually updated vaccines.”
I wonder if this is why Dr Fauci is emphasizing the need for therapeutics as higher priority than vaccines at this point? I should say though, mathematical biological models like the ones in this study are not something I feel very well equipped to evaluate. How often are such models wrong? What are the incentives for the company associated with these authors, “Fractal Therapeutics”? Obviously Harvard is Harvard, but I just can’t understand why smart people aren’t talking about this stuff. Murti-Bing pills?
I disagree. It has been shown over many years of research that viral mutations may be driven by both antigenic drift as well as selective immunological pressures, with the question being more the degree to which these factors influence mutation in different viral species.
Not to present an argument against vaccination, rather an argument against making blanket statements that fail to accurately represent the current state of collective knowledge on the subject, to wit: We do not know with any certainty the degree to which either of these factors drive SARS-CoV-2 mutations. A naked statement that the un-vaccinated population drives the mutation rate of this virus is nothing more than speculation; issues surrounding a field of study as incredibly complex as this may not ever be definitively put to bed through analysis of (conflicting?) study outcomes- let alone through arguments made in the commons of popular science.
I don't argue that emerging SARS-CoV-2 mutations are driven more by one factor or the other, I argue that we do not know the degree to which mutations are driven by 'random' antigenic drift vs selective pressures. Unfortunately, the issue has been politicized to the point where study outcomes that suggest dominance of one over the other are likely to be attacked or even ignored, regardless of the strength of study.
Citations? Efforts to find evidence here prioritized time invested over strength- this may not represent the best arguments out there, however it took only a scant few moments to gather, and points to a much larger body of literature supporting the position that both antigenic drift and selective immunological pressures drive viral mutations (SARS-CoV-2 being no exception) and that we do not know the degree to which each is a factor... and therefore stating OR implying that the un-vaccinated population drives the viral mutation rate in this pandemic is inaccurate. Once again- we simply do not know.
CF
"Given that the antibody response to the spike protein is so focused, could mutations in these restricted sequences lead to a less efficacious vaccine, if the human immune response is specific to the vaccine sequence? These mutations might be driven by antigenic drift, or by selection, either during natural infection or due to the vaccine itself. When a virus is grown under the selective pressure of a single monoclonal antibody that targets a single epitope on a viral protein, mutations in that protein sequence will lead to the loss of neutralisation, and the generation of escape mutants. This sequence of events has been shown in the laboratory for polio, measles, and respiratory syncytial virus,7 and in 2020 for SARS-CoV-2.8"
https://www.thelancet.com/journals/lanres/article/PIIS2213-2...
McCarthy, K. R. et al. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science 371, 1139–1142 (2021).
Plante, J. A. et al. The variant Gambit: COVID’s next move. Cell Host Microbe 29, 508–515 (2021).
Ravindra Gupta, Steven Kemp, William Harvey et al. Recurrent independent emergence and transmission of SARS-CoV-2 Spike amino acidH69/V70 deletions, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-136937/v1(2021).
The point made by GP is that the current mRNA vaccines are actively designed to illicit a highly targeted immune response targeted towards the spike protein [1].
> That's why anything that would make real progress has to happen quickly and broadly, without large left-out pockets
Assuming you mean 100% vaccine coverage, this is the opposite conclusion that the authors of this paper came to [1].
Citing [1]:
- "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape"
- "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities"
[1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/
Selection pressure to see what variants become dominant happens later. They aren't being actively "designed" in any sense.
That's why anything that would make real progress has to happen quickly and broadly, without large left-out pockets (not that rejecting a vaccine is any worse than not being offered one in the first place, here - that's the issue that is mostly being ignored for now, since we have no current solution).