I feel entitlement-vibes [LWN.net]

I feel entitlement-vibes

Posted Jan 30, 2025 11:04 UTC (Thu) by nix (subscriber, #2304)
In reply to: I feel entitlement-vibes by bluca
Parent article: FOSDEM keynote causes concerns

> I am well aware of how the health service works in my country, thank you. Vaccine procurement, authorization, etc, is not devolved, and is largely dependent on the JCVI, so the only thing the SNHS can decide is whether to make them available for free or not and to whom, but private pharmacies can sell it (or not) to paying customers independently of it.

In large parts of England they have elected not to -- the cost of doing so is too high, and it was literally driving pharmacies bankrupt (which you'd think would have made it obvious that there was a lot of demand...). So they almost all stopped. I think last I checked there were two left providing vaccinations in all of Cambridgeshire, both with huge backlogs.

> This is illiterate nonsense. "Natural immunity" fades within months from the infection.

There are two distinct things going on here. Antibody levels drop fast -- this is a *good thing* because if you had the immediate post-infection level of antibodies to every disease you ever caught your blood would be a thick soup at best. The level you get after antibody ramp-up is the level you need to drive out an *established disease*, not defeat a newly-landed one). Antibody levels are really easy to measure, so have got most of the attention.

What probably does not fade so fast is T cell recognition of viral antigens: T cells have a remarkably long life (it can be decades!) and remain receptive as long as they live -- but can be killed off by other things, can go nuts attacking some other disease they are also receptive to and get exhausted doing that, etc. But if they survive all that, they will probably protect you from getting actually killed by covid for a long, long time. Not always -- this is statistical -- but probably.

Neither of these things really kick in fast enough to prevent viruses that replicate in the respiratory tract from getting in there, replicating, then going straight back out to infect someone else. That sort of immunity is very hard to attain, which is why no covid vaccine to date prevents transmission, and why the common cold is so incredibly hard to stop.

But, y'know, it's not just getting killed I want to be protected from! I don't much want to land in bed for three weeks feeling like death either, like I did last time I got covid (let alone the two months of being too enervated to do much work). And *that* is helped by reducing exposure, by, say, getting people who might be infectious to wear masks, or just not going to FOSDEM.

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I feel entitlement-vibes

Posted Jan 30, 2025 11:46 UTC (Thu) by paulj (subscriber, #341) [Link] (1 responses)

Another factor is the imprinting if you keep being exposed to the same antigen. Your humoral immune system works on a form of rapid evolution, where B-cells (which later will produce antibodies, when stimulated) are "trained" and selected for in germinal nodes/centres (GCs). Your B cells go through rapid evolution in the GC, to try adapt to antigen collected in the GCs, with a selection pressure applied (at least in part) by T-cells. Different lines of B cells in the GCs will evolve to recognise different features of an antigen - it's a stochastic learning process. You end up with different lines of B-cells that have been trained to recognise different parts of different antigens _in different ways_.

There is evidence that repeated exposure to the same antigen will lead to this system becoming very specifically trained to that antigen - "imprinting". With rapidly evolving pathogens, with rapidly varying antigens, this is not per se a benefit.

E.g., (and without making a specific point about any particular disease), repeated immunisation with a vaccine that contains (or causes the manufacture of) 1 specific, unchanged, antigenic protein of a pathogen, is likely to lead to a population of B cells with a stronger bias towards that antigenic protein (kind of like doing ML with a large data-set except it's strongly biased to one feature). Yet, if that pathogen evolves rapidly in the wild it is likely to lead to mutations in that antigenic protein so as to evade those immune responses trained to that old version of that protein.

It is probably better to train your immune system with a /spectrum/ of antigens. Not just 1 protein from 1 version of a pathogen that was in the wild 3+ years ago (and has evolved numerous new, slightly different, lineages since). The literature suggests this is the case across a number of diseases, where we have some data on repeat exposure to unchanged v evolved antigens (be they from vaccinations or infection). That is NOT to say there is no value in immunisation by vaccination! But it does suggest there may be /diminishing/ value - even sometimes negative value - in repeated vaccination with old antigens (in the general sense). There is /some/ evidence in the literature this may be the case for ever-repeating covid19 vaccinations (all in the west present a subunit protein of the spike, with a very infrequently updated version of it). In tandem with vaccinations, we all are anyway - unavoidably - exposed to the full pathogen, through minor infections, when it comes to highly infectious respiratory pathogens such as SARS-CoV-2, so we will still get that wide exposure.

Then there are also T-cells, which directly kill pathogens, and also help mediate B-cell evolution. Some will last you pretty much a lifetime, as you say.

Things here are fascinatingly complex. There are many systems and interactions. There are trade-offs. Sadly, clever people on both sides prioritise politics over educating themselves and reading actual scientific information - instead getting their knowledge largely from popular political media, which is nearly always laughably simplified to point of just being incorrect - and that's true be it "Colbert" or "Fox News".

There is far too much knee-jerk idiocy on /both/ sides.

I feel entitlement-vibes

Posted Jan 30, 2025 11:56 UTC (Thu) by paulj (subscriber, #341) [Link]

Oh, "immune imprinting" and "original antigenic sin" are interesting terms to search for in your favourite tool to google scholarly articles - and then follow the thread of higher-prominence citing articles. There's a body of work on this in immunology predating 2020, and so generally free of the politicised stuff post-20, and it's interesting and informative.

Complexity. Trade-offs. They abound.

I feel entitlement-vibes

Posted Jan 30, 2025 12:04 UTC (Thu) by paulj (subscriber, #341) [Link]

> Neither of these things really kick in fast enough to prevent viruses that replicate in the respiratory tract from getting in there, replicating, then going straight back out to infect someone else. That sort of immunity is very hard to attain, which is why no covid vaccine to date prevents transmission, and why the common cold is so incredibly hard to stop.

There is /some/ evidence that nasal spray vaccinations have a degree of better efficacy for preventing covid infection than injected vaccinations. There are many different kinds of T-cells, and 1 variant is specific to the mucosa - a kind of front-line of defence, at the point of entry for respiratory infections. Nasal spray vaccines appear to stimulate immune responses in those mucosal cells a little bit better than muscular injections.

Been a while since I read into this though, and the evidence base was still preliminary and weak/suggestive at that point. I have not followed evidence since, and I do not know if stronger evidence now exists and if so whether it confirms or contradicts the earlier. (I don't think nasal spray covid vaccinations are widely used yet (??), in which case there is unlikely to be any strong evidence yet either).