[meekrohprocess]

So does this mean that the mRNA vaccines are probably going to be like flu vaccines, where they have to predict which variant will dominate each season and adjust the doses accordingly?

Can other options like the adenovirus-based or J&J ones be expected to cover a broader spectrum of mutants?

(And why are so many people downvoting these questions? I'm genuinely curious, and I really tried not to offend any sensibilities, but did I say something wrong? Oh god why do people always hate me so much? Is it possible to say or do anything right anymore? Maybe it's time to quit social media...I'm out, y'all are cruel.)

[jfoster]

I think you're probably being downvoted (note: not by me) because the way your comment is written makes it sound a bit like you're assuming the Oxford-AstraZeneca vaccine is an mRNA vaccine when it's not.

[Closi]

The good news though is that it does have some sort of platform technology that means it can be quickly altered.

[corty]

Problem is, the platform is a vector virus that causes immunity against the vector. So while you can create a new vaccine for the variants, you either cannot reuse the vector or you can't vaccinate old-variant-vaccinated people against the new variant. The body would kill the vector too quickly, limiting exposure to the payload too much.

In that respect mRNA vaccines or live vaccines have an advantage.

[chimprich]

I don't think that's correct (but I'm willing to be corrected by an expert).

I believe the immune response is mainly triggered by the spike protein. If the spike protein of the variant is different enough to cause a degree of vaccine escape, then the spike protein of the vaccine should be different enough to not get immediately cleared from the body.

This is based on what I've understood from listening to interviews with prof. Sarah Gilbert, head of the Oxford team.

[valarauko]

The parent is referring to a valid concern that with repeated doses (like from a subsequent booster), the mild antigenicity of the vector virus itself can be a problem. The Oxford vaccine uses a Chimpanzee adenovirus, which can infect human cells but not replicate inside them. There after delivering the vaccine payload, over time the protein coat of the vector will be chopped up and presented to the immune system, as are all cellular proteins. As you are unlikely to have been previously infected with a chimp adenovirus, it should elicit not much of an immune response, but the body will see it as foreign and start raising antibodies against the adenovirus proteins (adenoviruses have their own versions of "spike" proteins, among others). Of course, we would expect most of the immune response would be against the corona spike payload, but some fraction would inevitably be for the adenovirus as well.

When you get your second dose, you already have some antibodies against chimp adenovirus, which will potentially destroy some of the vector before it has a chance to be taken up by your cells. Third or fourth booster shots against coronavirus variants using the same chimp adenovirus vector would trigger worse reactions, destroying some portion of the vector before the payload can be delivered. The Russian Sputnik vaccine tries to reduce this likelihood by using different adenovirus vectors for each dose.

[bluGill]

The good news is there are more than enough vectors to choose from.

[bencollier49]

They said they'd have a new one by Autumn...

[e_y_]

It's not clear how much it'll continue to mutate. Since this is a brand new virus, it's had 100M+ people so far to experiment on, and clearly the early versions were not as efficient at spreading as the newer variants.

Once we have herd immunity through vaccination (since natural immunity is rather hit-or-miss) I would hope the rate of mutations slows down significantly.

[cortic]

Logically i would have thought the opposite would have happened, since natural immunity is mostly to the nucleus protein (difficult to mutate), and vaccine immunity is based on the spike protein (easy to mutate). I would have thought any partial vaccine immunity would increase mutation rate.

Also been worried that mass vaccinations might short-circuit the mutate to less severe variant process that happens in nature. By taking the advantage away from the current spike configuration we might give an advantage to a worse variant that would naturally have died out (out compete by its parent variant)..

Disclaimer; I'm more qualified to write a science fiction novelette on this theory than a medical paper, so take all this with a big grain of salt.

[e_y_]

It's probably too early to say if the vaccines have had any effect on the mutation rate, since wide-scale vaccination has only just started ramping up.

You'd think it'd be easier to say whether people are getting reinfected after catching COVID the first time, but the testing data is sparse enough that there doesn't seem to be any confirmation on whether it's widespread or just isolated cases. Most notably in Manaus, Brazil, where one of the new variants has been spreading.

I'm definitely not qualified to make anything other than wild guesses on this subject, but everything I've read suggests that scientists are scratching their heads as well. Conventional wisdom is that the spike is the easiest to target, so whether the human immune system picking the N protein is a mistake or brilliant move seems to be up in the air. Some reading: https://www.nature.com/articles/s41577-020-00480-0

Mutating to a less severe variant: Given that SARS-CoV-2 already has delayed symptoms and a high percentage being asymptomatic cases, I'm not sure there's much pressure to make it milder. Also the overall spike design is what gives SARS-CoV-2 its higher infectiousness compared to the original SARS, so one would hope that mutations to it (to avoid existing antibodies) would tend to make things less effective, although unluckily the virus has been discovering some new configurations that are both more infectious and also less protected against by the existing vaccines (especially the 60-70% ones). Paper on infectivity of variants: https://www.cell.com/cell/pdf/S0092-8674%2820%2930877-1.pdf

[dehrmann]

One thing that will be interesting, and rather unusual, is we have different approaches to vaccines being deployed within months of each other.

[stirlo]

The Oxford vaccine which was paused is not mRNA it is adenovirus.

GSK has recently announced plans to produce a multi-valent mRNA vaccine for distribution next year so mRNA is not necessarily limited to a single variant. https://www.gsk.com/en-gb/media/press-releases/gsk-and-curev...

[Closi]

It’s worth noting that the Oxford vaccine can be quickly altered too, as it’s based on a platform technology. They suspect a version with variants can be in production and being rolled out by August.

[mxcrossb]

I wonder though if the really good trial data of the MRNA ones mean they’ll be able to do just safety trials (nothing on effectiveness) in the future, while the Oxford collaboration will be closer scrutinized.

[bedobi]

Thanks for sharing this piece of info, I had no idea, seems like great news!

[powerapple]

What you are saying might turn out to be true. There was a report on how Chinese vaccine was good in some countries but not doing well in Brazil, it may be related to mutation as well. If the virus mutates fast because countries are not controlling the spread well enough, current vaccine may be less and less effective in time. I am sure the producers are updating their vaccines in meantime. It will take time and the production will take time as well.

Unfortunately mRNA vaccines will not be a universal solution for all countries, it will only be applicable for a few rich countries.

[Ulrich2]

Good news: Curevac needs only a standard refrigerator for storage. Hopefully it works. Also, Biontech is working on a V2.0 with less cooling required.

[sjg007]

Yes most likely we will have a yearly vaccine or cocktail of vaccines for covid. Not sure if it will be mRNA specifically but most likely it will be.

The flu shot for example isn't an mRNA vaccine but rather the strain they think will be dominate.

Regardless, we will be wearing masks and social distancing for a long time (years) to come.

[ghaff]

Boosters are probably inevitable but once people are widely vaccinated, most are going to get on with their lives in a largely pre-pandemic way.

[ls612]

I feel like it is optimistic to think that we will be allowed to live our lives the pre pandemic way. These new strains will be trotted out as a good excuse to keep these restrictions around much longer.

[ghaff]

IMO no government in the US is going to indefinitely ban large indoor gatherings, indoor dining, bars, schools/universities as usual, physical conferences, etc. And any "rules" notwithstanding I fully expect that when summer rolls around and a lot of people, especially the more vulnerable, have been vaccinated whether it's imperfectly or not are going to back to beaches, bars, concerts, etc. At some point, it's just another disease of which there are many that sometimes kills people.

[sjg007]

All pandemics end eventually, but it depends right? It depends on hospital capacity and how infectious and lethal the variants are and if the vaccines work and how fast the spread is. Not to mention super spreader events.

Covid wild-type was/is bad enough to crush global hospital systems so that's really a big issue. It will take years to train more doctors and nurses to run covid wards if that's something we decide to do.

Also things won't go back to normal because our hyper-globalization and world wide travel has definitely increased the risk of pandemics. So we have to think of the next unknown one, use technology to prepare as well as implement risk reduction processes. Covid testing for international travel will probably never go away.

[koheripbal]

The moment we discovered that numerous other species are transmitting the illness - made yearly shot inevitable.

[sjg007]

We've know this is true for generations...

[MattGaiser]

The Oxford one is not an mRNA vaccine.

[peter_retief]

I up voted you, the voting system on HN is a mystery to me.

[bumbada]

I agree that people on HN downvote reasonable opinions and questions that do not go against HN guidelines.

It is the reddit effect. At first Reddit was like HN populated with highly educated people. As it got more and more users it democratized: The vote of a know-it-all 16 years old is the same as the one from a PhD in the field. In fact there are thousands of non experts for each expert, so they always win in a public space.

We add to that that we are using text, we do not carry intonation and other emotional information and lots of people will misunderstand whatever you say.

So the more popular a place like this becomes, the most degraded it becomes.

Do not take that seriously. I had great karma when I posted my real identity years ago and now lots of my comments are downvoted too, and I am the same person. I did not care then and not care now.