Hacker News Reader

Comment by samspenc | Hacker News Reader

Trying to understand something here: when COVID-19 first came out, there were reports that it would be difficult to produce vaccines for it because it is was a mRNA virus (as opposed to a DNA virus for which it is easier to produce a vaccine for.) One of the reasons I remember reading was that a vaccine could work for one mRNA variant, but not for the multiple variants that mRNA viruses are known to mutate into.

Is this what is happening? The current vaccines are effective against existing / known variants, but the new variations / mutations would require new vaccines?

View on HN

Sort of. The thing is, while there are already variants out there that impact immune response, it's not like a single mutation is a vaccine escape. It's more like the vaccines go from 95% efficacy to 75% efficacy.

Now, I'm no biologist but I would imagine DNA viruses are easier to vaccinate primarily because they have lower mutation rates than RNA viruses. However, even within RNA viruses, there's differences in mutation rates. Influenza mutates so fast (and is allowed to replicate out-of-control most of the time) to the point that vaccine escape happens within a year or so - that's why you need a new flu shot every year. As far as I'm aware, COVID-19 mutates slower than the flu, so vaccine escape will take longer.

Out of the three COVID-19 vaccines out there, two of them use an mRNA vaccine platform. This isn't because you need to match mRNA viruses with mRNA vaccines, but because it's just an extremely versatile platform to work with. In fact, for Moderna, stopping a worldwide pandemic was just a side project. Their actual goal was to produce custom cancer vaccines tailored to an individual patient's tumors. You can do this because the vaccine is just some genetic material and some nanoparticles to get it into cells. Your body itself makes the actual antigens that your immune system then fights.

So what will ultimately happen in the event of a vaccine escape is that Moderna and Pfizer will tweak their vaccines a little and the FDA will fast-track a new roll-out of the modified shot after Stage 1 testing. They already do this for flu vaccines - it's the only reason why we can even vaccinate against the flu in the first place. And as far as I'm aware, Moderna and Pfizer are both already trialling booster shots. Not so much because they expect a vaccine escape, but because they expect immunity to wane regardless of how fast the virus mutates.

> Influenza mutates so fast (and is allowed to replicate out-of-control most of the time) to the point that vaccine escape happens within a year or so - that's why you need a new flu shot every year.

No, it's because the yearly flu shot only includes a couple of the viruses out there. They take a best guess in the spring as to which ones will be the most prevalent in the fall and start production on those.

From what I remember it's limited to only a few for two main reasons: Cost and some of the vaccines aren't actually compatible with each other (so you can't put them in the same shot).

This. The influenza variants that "arise" next year are almost certainly circulating at low level now, and not targeted by this year's vaccines.

If we vaccinate everyone, aren't we selecting for the virus mutations in which the vaccine doesn't work, can we possibly make virus more advance this way?

It depends on what you mean by “more advanced”. More lethal? Easier to transmit?

In any case, the answer is “maybe”. By vaccinating, we cannot be sure of what is actually being selected for. We only have an idea of what is being selected against.

Being a novel (new) Corona-virus, nobody actually knows the extent of possible mutations. This is a strong argument against it being a weapon. However, it's impossible to contain everywhere, though we should perhaps make the attempt.

My understanding is that lethality and transmisability are typically a one or the other type situation. Viruses like HIV and to some extent COVID that kill their host effectively but slowly are rare. The typical case is to either multiple quickly inside one host (i.e. kill the host quickly) or move quickly from host to host (i.e. spread rapidly without killing the host because you need the host to be a vector)

> but the new variations / mutations would require new vaccines?

I'll just poke at this part since the other responses are good on the rest:

It's not "would", it's "might". The mRNA vaccines, for example, train your body against the spike protein - a very specific piece of the virus. The vaccines would still work against any mutations that don't change that piece of the virus, and even for the mutations that do change it, the change might not be big enough to have an effect.

You got it right. Generally speaking, RNA viruses (without the “m”) have higher mutation rates than DNA ones. Therefore the possibility of a vaccine-evading mutation arising in their genome is higher as well. However, predicting a priori the effect of such a mutation is difficult, because it depends on many factors.

For instance, the mRNA vaccines are optimized to generate antibodies against the SARS-CoV-2 spike protein in the prefusion state. If a mutation alters this conformation the immune response elicited by the vaccine might be reduced or even abolished.

In addition to that, mapping the mutational space of the virus is experimentally challenging and computationally expensive, so there’s no easy way to be prepared against potentially detrimental mutations.

Reply on news.ycombinator.com