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Comment by kjakm | Hacker News Reader

Interesting shift in strategy. Instead of giving the second dose within a few weeks of the first they’re going to allow up to 12 weeks between doses. Allows them to get more widespread level of some protection with dose 1 before later boosting protection.

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They are considering the same strategy in Belgium, but with even bigger gap. It seems that it’s the only way to achieve at least some herd immunity before summer.

Belgium is going to investigate smaller doses to go faster too.

It looks really promising, but investigation is required.

We tried the same thing, in Canada, with the yellow fever vaccine. There were shortages about 6? 7? years ago, and 1/5th dosage was consider a stop-gap, by conveying some immunity.

(And, better outcomes overall, too)

Not sure how all of that wound up, but:

https://www.who.int/emergencies/yellow-fever/mediacentre/qa-...

edit: For clarity, there wasn't an outbreak in Canada, but just shortages if you wanted to travel, and needed the vaccine.

> just shortages

I had the yellow fever vaccine last year in America. I received an, otherwise identical, Europe-manufactured vaccine instead of an American one because the shortage is on-going.

Supposedly identical, yet the European one (French?) wasn't approved for use in Canada yet.

Your response made me think back to my research a few years back. Mostly, because I am surprised that there are STILL shortages! For more than half a decade?!

Found this:

https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-S...

Quote:

Sanofi Pasteur has YF-Vax multi-dose vials and single dose vials on back order and the company estimates product will be available in 2021.[1]

Sanofi Pasteur has worked with FDA to make another vaccine, Stamaril, available in the US under an investigational new drug program. Stamaril is yellow fever vaccine manufactured by Sanofi Pasteur in France. It is not licensed in the US.

This, I recall. I also recall some more research, which I cannot find now, in that there were different production methods between the two vaccines. Hence, the lack of quick approval. Yet Yellow Fever is crazy spreadable! And still the vaccine is not fully approved in the US/Canada?!

I recall reading a report, where one person with yellow fever was briefly in an airport lounge. 20 minutes later, a few people passed through, and most caught it! Just... it makes COVID look like a joke, yet here governments are dragging their heels over approvals due to production methods over the same strains?

And those production methods / that company has been making and administering that version for decades? To hundreds of millions?

It really makes you think a bit about COVID approvals. Talk about a change of heart.

(I am a Belgium resident)

I think the only reason they're considering this in Belgium right now is because they are unprepared in the extreme. They have frankly pissed away their time instead of actually preparing for the vaccine, the past nine months.

The current vaccination rollout plan leaves healthcare workers unvaccinated until march. HEALTHCARE WORKERS.

https://www.brusselstimes.com/news/belgium-all-news/147133/c...

There's been some pretty severe backlash to that, and rightfully so (I don't know of any other country that isn't vaccinating its health workers in the very first phase alongside senior citizens). I ran some numbers the other day and if you're distributing the vaccines exclusively via the 40-ish Belgian hospitals that can store the Pfizer one (and only 6 in Brussels), then there is no way to achieve herd immunity before end of 2020. The only real solution to that is to allow for more widespread distribution via pharmacies. (Yes, medium-term storage is an issue, but AIUI the Pfizer vaccines can still move around after thawing for some time so short term redistribution is possible if you've prepared for it).

So they're trying whatever they can to compress the timeline. It's not necessarily a bad decision, but it's a workaround to a worse one.

This is happening in the US as well, and now they're acting shell shocked at receiving 2-3 million doses because that is actually indeed a lot of doses which means you need lots of trained people on how to handle them and inject them. This is gonna take a long time. Hopefully Biden will scramble more people and resources. Depending on corporations as the sole distributors is a bad, bad idea.

Yes, and all the parties from the beginning of summer till days before new lockdown. I don’t know how it goes in other countries, unfortunately common sense is anything but common.

Also I’ve read that “Belgium accounts for 25% of Europe’s biotech”. I wonder why there’s no domestic vaccine yet given such R&D capacity.

Recent reports mention 95% effectiveness for the Oxford-AstraZeneca vaccine if the doses are taken 3 months apart, which would be great if confirmed.

https://www.businesstoday.in/current/economy-politics/oxford...

https://www.thetimes.co.uk/article/covid-vaccine-boost-for-m...

they always seem to find additional data supporting this or that. Idk, to me it seems like their reporting is literally all over the place, how did they confirm 95% effectiveness? what's the trial-size, is it also 30k participants like the others? What's the age-distribution of those that took part in this 3-months trial, there are a ton of unknowns with that vaccine, and neither Oxford nor AZ are particularly helpful with clearing those doubts atm.

They have in many ways been more rigorous and transparent than other vaccine trials (weekly swab testing of all subjects, publishing the paper first rather than in the media first, being honest about mistakes made). They don’t control the media reporting.

That said it seems the group who received smaller doses by mistake was only 1300, not sure where they got the data on 12 weeks but presumably it’s also a small number or they’d be going with that for everyone.

Things should become clearer over time and I hope they can shift to the smaller doses first as it’d give us double the number of initial vaccinations when supplies are limited.

the just tried to fit in numerous trials into a single trial, whereas Biontech/Pfizer and Moderna were super clear about their trial-architecture and data (same 2-dose regime, given 3 weeks apart), we seem to have a ton of small trials with different data for that Oxford/AZ vaccine. Those 1300 participants who got the half dose full dose vaccine also turned out to be significantly younger than the other group who got the two full-dose regime, making those two groups really difficult to compare (apart from the fact that they were also differing in size)

Now we have a new number out there, 90% if the two doses are given 3 months apart, does anyone here now what the trial-size was? the age distribution? The statistical significance for that finding?

From the news report it's 95%, not 90%. Presumably the data about sample size etc. will be available when they publish. You can't reasonably expect that level of detail from a news article reporting prior to publication.

Don't forget that the BioNTech/moderna trials weren't really comparable - they relied on self-reported symptoms to trigger checks for infection. That is likely to lead to a higher apparent efficacy at the same underlyng efficacy.

By now it's clear that for all three vaccines regardless of the exact efficacy of the vaccine, the chances of getting a severe case is greatly diminished. It's at least plausible that getting a vaccine reducings the severity of an infection in general; specifically that it might push what would otherwise have been a mild case into the asymptomatic (but infected) category. I don't know how large that group is, but given how many mild cases there are, it could be quite sizable. And those cases would not have been included in moderna and biontech/pfizer's efficacy numbers, but would have been included in the oxford/AZ trial's numbers.

So while I'm no expert in any of this, I think it's at least fair to say that it's not trivial to compare the efficacies reported from the two mRNA vaccines to that of the oxford/AZ vaccine, because of this difference in methodology. Including vs. mostly excluding asymptomatic cases will affect the numbers.

The point being? All of these trials have their limitations; the oxford/AZ trials may have had bumps (but nothing all that serious sounding), but they also have extra data in the form of asymptomatic cases. The comparison isn't straightforward.

that 62% number is for symptomatic cases, I think it was around 50% for asymptomatic cases - the different efficacy-rates are fairly comparable

That is a good point, I'd forgotten that bit ;-).

(ref: https://www.thelancet.com/journals/lancet/article/PIIS0140-6... vs. e.g. https://www.nejm.org/doi/full/10.1056/NEJMoa2034577 )

They gave more data to MHRA. Let's not forget that the data used for the Lancet publication was from November 4th.

And the Jenner Institute in Oxford doesn't do preprints or press releases for data, they go for publications (so that takes more time).

That said, I expect the missing information to appear in MHRA's guidance notes.

What would be interesting about that is what happens when people are not going to get the booster for various reasons.

Mutation?

Mutations happen all the time regardless of vaccines. The vaccine adds evolutionary pressure and will likely give an advantage to the bearers of particular mutations.

If the virus has a smaller base of infected people who grow it, there will be less mutations. From that point of view, the sooner all the world is vaccinated, the better. The risk of a new, more dangerous mutation decreases.

I think early data showed that you still get ~60% protection with the first shot (or was that for the Moderna vaccine?) Still, you get some level of immunity, booster only makes it higher.

The two dose studies provide incomplete information about the single dose efficacy — administration of the second dose ends the data collection for the first dose alone.

The data collection also includes the period of time that the body spends responding to the vaccine (so if you get the shot and get infected that day, the shot gets counted as not being effective).

And then on the other side of it, they don't have data on how long immunity from a single dose would last.

But it's likely that the Moderna and Pfizer vaccines have quite high effectiveness after the initial immune response.

Sure, while it's not perfect, the data for those 3 weeks between the first and second shot still can provide a lower bound approximation for immunity, which I assume is where the 60% comes from.

The point about how long single dose immunity lasts is fair though.

Why would they not get the booster?

Some will forget, some won’t realise they need it, some will get symptoms the first time and not want it. I don’t expect it will be widespread but humans will be human

Why do people miss their flight?

So much so that airlines can oversell a substantial number of tickets on any given flight and usually the plane departs with empty seats?

Why do people get divorced?

Why do...

You must not be a software developer

All that happens is that they have somewhat smaller protection for a shorter time.

Unless the vaccine or virus is very different from normal ones.

Good idea indeed!

Is this driven by the desire to vaccinate more people, or more to do with the logistics of vaccinating this many people?

I believe it's because preliminary experimental results suggest that the efficacy is greatly increased.

I can no longer edit this comment, but I was wrong. The reasoning behind the longer gap between doses is logistical, and attempt to get as many first doses in as short a time as possible. It is scientifically unfounded.

This is the way

The whole thing is ludicrous. This strategy also applies to the Pfizer vaccine. By having the booster further apart, it lowers its efficacy from over 90% to around 80%. Given the mistakes the UK government has made along the way, this just fills me with further dread for the situation (I have family there).

Prolonging the 2nd dose interval increases the level of antibodies elicited after the 2nd dose.

Dose Interval --> 28 days after dose 1 --> 28 days after dose 2

<6 weeks --> 8,734.08 --> 22,222.73

6-8 weeks --> 7,295.54 --> 24,363.10

9-11 weeks --> 7,492.98 --> 34,754.10

≥12 weeks --> 8,618.17 --> 63,181.59

from https://www.gov.uk/government/publications/regulatory-approv...

This is in the case of the Oxford/AstraZeneca vaccine. Not the Pfizer.

80% protection for 2 people is better that 90% for 1.

I would agree if this was for the general population but consider the most vulnerable are being vaccinated first. They should be treated with great care and priority and I think it’s unethical for the UK to lower their chances, especially considering the huge numbers of vaccines they are going to have over the coming weeks.

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