27 Comments
Dec 3, 2022Liked by Brian Mowrey

When I googled (although I used bing) "what is a leaky vaccine," what I pulled up was the distinction between a leaky vaccine and an "all or none" vaccine:

""Leaky" vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to "all-or-none" vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures." https://pubmed.ncbi.nlm.nih.gov/24895500/

So that author does not distinguish between leaky and sterilizing; they distinguish between leaky and "all-or-none." I will now need to read the rest of your paper (which will probably take me weeks) in order to see how this fits with "sterilizing" versus "non-sterilizing."

The first thing that occurs to me from this definition of leaky is that with a leaky vaccine plus incredibly high community prevalence (where I am in CA, the wastewater is worse than it was at the peak of Omicron), you are going to get a lot of leaks.

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Apologies in advance for only reading to footnote 1 and chasing a squirrel [imitates Boomhower] GD Internet click click click

The irony of reading that while hearing a commercial on the radio for the variant-killer bivalent booster.

https://www.aps.anl.gov/APS-Science-Highlight/2022-08-01/unraveling-sars-cov-2s-mutagenic-prowess-one-enzyme-at-a-time

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Your thinking in these matters continues to parallel mine. My background, however, is in computer science (BSCS plus 50+ years in the field; couldn't find a use for an advanced degree). There is a surprising degree of overlap. I became interested in the mechanisms of protein synthesis about 10 years ago, and it may have saved my life in 2021, if you see what I mean.

I can't pause for a lengthy reply today, but I'll challenge you with one question: Could your view of viral behavior offer a clue that they may have been _designed_ this way? It's surprising what can pop out when you revise your assumptions.

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And this..... don't forget that this was a single epitope vaccine. There's the question of sterilizing vs non-sterilizing, but also the question of how broad the viral epitope coverage is. I am guessing that, in reality, the mRNA's were always much less sterilizing vs. for instance Polio.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250780

"The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control. Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD? To answer this question, we combined an analysis of the RBD structure-function with an evolutionary modeling framework. Our structure-function analysis revealed that epitopes for RBD-targeting nAbs overlap one another substantially and can be evaded by escape mutants with ACE2 affinities comparable to the wild type, that are observed in sequence surveillance data and infect cells in vitro. This suggests that the fitness cost of nAb-evading mutations is low. We then used evolutionary modeling to predict the frequency of immune escape before and after the widespread presence of nAbs due to vaccines, passive immunization or natural immunity. 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. Predicted resistance timelines are comparable to those of the decay kinetics of nAbs raised against vaccinal or natural antigens, raising a second potential mechanism for loss of immunity in the population. Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities"

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I don't think there any absolutes here... it depends.... from 2015;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516275/

"Could some vaccines drive the evolution of more virulent pathogens? Conventional wisdom is that natural selection will remove highly lethal pathogens if host death greatly reduces transmission. Vaccines that keep hosts alive but still allow transmission could thus allow very virulent strains to circulate in a population. Here we show experimentally that immunization of chickens against Marek's disease virus enhances the fitness of more virulent strains, making it possible for hyperpathogenic strains to transmit. Immunity elicited by direct vaccination or by maternal vaccination prolongs host survival but does not prevent infection, viral replication or transmission, thus extending the infectious periods of strains otherwise too lethal to persist. Our data show that anti-disease vaccines that do not prevent transmission can create conditions that promote the emergence of pathogen strains that cause more severe disease in unvaccinated hosts."

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Can we vote for a show w you & JJ slow walking this w graphics maybe for folks in the bleachers?

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This was very interesting. Your analogies facilitate understanding greatly. Thank you!

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Dec 1, 2022Liked by Brian Mowrey

I fear you may need to find some other analogy to explain ideas as some of us have never played computer games and haven’t a clue what you’re on about!

On a separate note - I’ve just finished listening to ‘ Inventing the AIDS virus’ which seems to stop around 1995. The only other thing I think I know about HIV is that it infects CD4 T cells. What should I read next to get a better understanding? If it’s a ‘harmless bystander’ then why is everyone so worked up about it having parts incorporated into the SARSCov2 spike? Thanks!

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I am not a scientist but I do find this article's theory very interesting so I would like to ask my question even though it might already have been answered in a way I failed to grasp.

So what I am confused about is why there would be one single max fitness for each virus. Wouldn't there be a huge variety of max fitness when you look at virus - host combined? So for instance human cell ace2 expression variation might create subsets of people to whom one coronavirus spike protein mutation would be more fit and less fit for others. Then we have a whole bunch of little fitness 'holes' and when some pressure forces a virus out of one hole it may fall down into another, changing which subset of hosts it is better adapted to. It is still optimal but optimal is contingent on host-virus as a set.

I read about some experiment in chemistry that was related to quantum physics. They could balance some substance on a hill where it was exactly between two states. The slightest nudge including measurement would push it into one or the other. It would resolve to one of the two states and be stuck there. Why wouldn't a virus have a lot of these potential contingent optimal states and immune pressure pushes it up a hill of low fitness where it falls into a new hole of contingent fitness? So isn't optimal a moving target that is also dependent on host-virus subsets?

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Dec 1, 2022Liked by Brian Mowrey

Is Tony Honk just a clever clown-world themed parody, or is that the name it was actually released under in some places?

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