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Comment by yonaguska | Hacker News Reader

> 67% protective against symptomatic COVID-19 in clinical trials

I'm not a big fan of any of the current vaccines due to their low efficacy against variants, and especially because they trigger an initially weak immune response and are only effective against symptomatic covid-19. The initial weak immune response gives mutations more time to occur, in my rudimentary understanding. If this vaccine is only good at preventing symptomatic infection- does this mean it'll apply more selective pressure on even more variants?

I know that a Marek's situation is highly unlikely with Covid, but won't weak vaccines increase the probability of this happening?

As a young healthy person, I still think natural immunity is the best way to reach some semblance of herd immunity for groups not at high risk. This feels like prescribing incomplete courses of antibiotics.

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> I know that a Marek's situation is highly unlikely with Covid

Someone told me about Marek at work but I didn't find anything related to COVID vaccines, good or bad.

Do you have some sources that speak about it?

Sure. Here's a recent article by one of the authors of the 2015 paper on Marek, claiming that it is being twisted to support an antivax narrative. It also goes into considerable detail explaining the virological and immunological background:

https://theconversation.com/vaccines-could-affect-how-the-co...

Thanks.

edit: I don't know why you were downvoted your article is perfectly on point.

It's general to all vaccines, not specific to just COVID. The search term you want is "leaky vaccine".

Basically, when you have a treatment (a 'leaky vaccine') that prevents symptoms but not transmission, then the normal evolutionary constraint for a virus to become less-harmful (to maximize transmission) goes out the window - because anyone that's been vaccinated could just as easily carry a more-harmful version of the virus.

It doesn't always happen, and it's hard to predict when it will, but Marek's disease is an example of a worst-case scenario actually happening: when a leaky vaccine scenario allows the virus to mutate and become highly lethal.

> normal evolutionary constraint for a virus to become less-harmful (to maximize transmission)

I don't know why we're taking it for granted that maximizing transmission is the same as being less harmful. The delta variant seems both more harmful AND more transmissible (and developed in an area that didn't have vaccines yet last fall).

There seems to be a good case to be made that, say, ebola is too harmful to be super transmissible. I don't think we can say the same for Covid yet. The majority of cases have never been fatal, on the contrary, being transmissible is what's made it a public threat and mass scale killer already. "Transmitting it without symptoms" has been a thing since day 1.

You have to look at the reasons why this behavior is occuring: Viruses get less harmful if it improves transmission. E.g. if you are more active and have a higher rate of contacts, even if infected and sick with a certain strain, that strain has an advantage. With Covid, most of the transmission occurs before symptoms appear, meaning that the severity of the following illness is irrelevant to transmission. In that case, the virus has no advantage from being less harmful.

Also, simpler changes are preferred over more complex ones. Delta probably just has a mutation that allows it to reproduce faster after an infection, meaning that both infectiousness as well as severity of illness go up at the same time. Mutations that increase infectiousness but lower severity are usually more complex, so less likely to occur, especially if not selected for.

> The delta variant seems both more harmful AND more transmissible (and developed in an area that didn't have vaccines yet last fall).

I left it out of the initial explanation for the sake of brevity, but there's several outcomes from a leaky vaccine. Two of them are: increased lethality, and adaptation to vaccines, requiring new vaccines to be developed.

So yeah, the delta variant makes it look like we might be dealing with a leaky vaccine scenario.

Sorry I wasn't clear: I have read about Marek but what I didn't find is can it happen with COVID vaccines or not.

Oh, gotcha. Here's a source that might help.

> There is a theoretical expectation that some types of vaccines could prompt the evolution of more virulent (“hotter”) pathogens. This idea follows from the notion that natural selection removes pathogen strains that are so “hot” that they kill their hosts and, therefore, themselves. Vaccines that let the hosts survive but do not prevent the spread of the pathogen relax this selection, allowing the evolution of hotter pathogens to occur. This type of vaccine is often called a leaky vaccine.

https://journals.plos.org/plosbiology/article?id=10.1371/jou...

Basically, it all comes down to whether or not the vaccines prevent transmission. If they do, we're all good. If they do not, we might be in trouble. It looks like they do not.

@raphlinus posted a link from the author of the Marek study, apparently he's not worried about it.

https://theconversation.com/vaccines-could-affect-how-the-co...

And there's others who are worried.

More to your point, though, I'm more interested in the peer-reviewed stuff than op-eds.

Remind me of what natural immunity is supposed to be good for, if not for preventing disease.

> especially because they trigger an initially weak immune response

Do you have any citations on that? Because it doesn’t match with my (admittedly rudimentary) understanding of how the vaccine works.

> As a young healthy person

I personally worked with a "a young healthy person" with your attitude. He's dead now. This is not your average cold we're dealing with.

Most vaccine boosters are spaced out 6+ months, but the emergency nature of the pandemic forced the trials to only space them out 3-4 weeks. All of the data is showing that a 6-8 month booster will offer a more robust protection. Further more, a delta or any specific tailored booster is trivial with mRNA tech.

If most vaccine boosters are spaced out like this, then I think we should continue doing this. Additionally, we should be factoring in previous exposure to covid before administering vaccines. Especially considering the increased risk of adverse vaccine reactions if you have already been exposed to covid19.

As stated in a previous comment, I indirectly know four healthy young, that died shortly after taking their second shots.

> I'm not a big fan of any of the current vaccines due to their low efficacy against variants, and especially because they trigger an initially weak immune response and are only effective against symptomatic covid-19. The initial weak immune response gives mutations more time to occur, in my rudimentary understanding. If this vaccine is only good at preventing symptomatic infection- does this mean it'll apply more selective pressure on even more variants?

I would assume the average hospitalized case has a longer course than the average non-hospitalized one - in which case, a vaccine that reduces risk of hospitalization seems to also reduce risk of mutations being spread on (since the time for mutations to develop and reproduce in a person is shorter).

> young healthy

Auckland, New Zealand is currently trying to stamp out an outbreak of Delta.

60% of those hospitalised are under 30 years of age. I’m not sure that relying on being young is that helpful.

https://i.stuff.co.nz/national/health/coronavirus/126218288/...

I am vaccinated but to be fair, that article is not a great rebuttal: it’s only a total of 34 hospitalizations and it doesn’t indicate that those young people were healthy. For all we know they could be cancer patients.

> that article is not a great rebuttal

For sure. It’s the bunch people it hit when it got loose here. It was just the first thing that came to mind when the “I’m young and healthy” argument popped up.

It’s quite early in the piece for good data, but ‘younger, sicker, quicker’ seems to be the takeaway.

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