Longer interval between Covid-19 Pfizer vaccine doses boosts immunity | Hacker News Reader

Longer interval between Covid-19 Pfizer vaccine doses boosts immunity

ncl.ac.uk

75 pointslnyan62 comments

In my country, we had 6 weeks between the doses. The main reason was shortage of vaccines, of course; nowadays the 6-week interval has been abolished and you can actually get the second dose earlier if you will, b/c "peak jab" is over and further interest wanes.

I am one of the "six week vaccinees", which sits just in the middle of the two sets studied in this paper. I wonder what the results for 6 week delay are.

Accidentally, Delta does not seem to be a problem yet in my country. IDK if it is luck, an early phase of a future wave or an effect of Pfizer doses being given 6 weeks apart, but our current Covid numbers are much more moderate than expected.

What country, if you don’t mind me asking?

by the nickname i'd assume czechia

Uhhh, has anyone read the article rather than confirming their confirmation bias...The header after the title is literally "One of the world’s most in-depth studies into Covid-19 immune response to vaccines shows a short and long dosing interval of the Pfizer jab generated strong antibody and T cell immune responses." Which means get both of your shots, regardless of gap. Evidence suggest longer gap gives better long term immunity but you are more vulnerable between both doses which can be can issue during an active pandemic. The article never suggests the "optimal" dosing schedule.

This is of course exactly what was expected, and why First Dose First was so clearly the right strategy until countries had plenty of supply. Good for the UK recognizing this early. The US hasn't.

What if it had gone the other way, and longer intervals made the vaccine significantly less effective?

I do agree with you on the whole, but for me it’s a very difficult choice, not an obvious one.

A few months ago I remember there were interviews and articles with immunologists and virologists. There seemed to be a consistent sentiment with many of them at least that the Pfizer and Moderna protocol intervals were kind of suboptimal from an immunology perspective. The conclusion was that many in the field saw it as obvious that the two companies were trying to maximize the probability of vaccine efficacy in as short of period of time as possible (I don't think they saw the companies as acting immorally, just that they saw it as not making sense unless you understood the time constraints). Many of the people interviewed commented that with unlimited time and lack of public health constraints, they would have expected smaller doses given longer apart.

I guess my point is, I'm not an expert in this area but there was a lot of chatter earlier that this was kind of predictable or something.

That would be unexpected. Not impossible, but improbable. Think about it this way: do you know of any other vaccines with 4-week intervals? If all other vaccines use longer intervals, what are the chances that this particular vaccines needs a shorter interval?

The decisions made in UK and Canada to delay the second dose were not a random choice. They were expected to work based on the body of knowledge we have from other vaccines and what we know about the immune system. It was by no means a certainty, but a strong probability. And it paid off.

Bexsero (MenB) is two doses given 4 weeks apart.

For children receiving their first vaccines for the flu (whether inactivated or live), it is recommended they receive two doses 4 weeks apart.

Lots of the early childhood vaccines have minimum spacings of 4 weeks, but are given at 2, 4, and 6 months simply because of standard pediatric followup visit schedules: DTaP, Hib, IPV, PCV13, and Rotavirus. HepB has a first dose at birth and the second at 4 weeks -- 2 months.

HPV is available in a 3-dose series with 4 weeks between the first two doses.

Even Bexsero vaccine has recommended interval of at least 1 months or 2 months, not exactly one month or at most 1 month. It seems to be consistent with longer intervals being ok.

https://bexsero.ca/content/dam/cf-pharma/bexsero/en_CA/docum...

It wouldn't have mattered.

The human trials had already shown that just one dose of Pfizer has an efficacy of 89% after 15 days. With a fast-spreading pandemic, the priority is to get as many people on their first dose as possible. This both starts to reduce the rate of infection, and also reduces the death rate.

The long-term effectiveness isn't a priority at first for the most developed countries. If necessary they can just order more vaccine after a few months and run a booster campaign later in the year. Cost isn't an issue.

I think you could argue that it has broken down a bit with Delta, as the first dose provides very little protection there.

Edit: Nevermind, I was wrong- apologies!

https://www.forbes.com/sites/carlieporterfield/2021/07/21/st...

From the article you posted:

> Two doses of the Pfizer vaccine had an effectiveness of 93.7% at preventing symptomatic alpha infections, and 88% for the delta variant.

[..]

> However, the effectiveness of the vaccines plummeted if a patient had only received one dose of either vaccine: the study found both to be just more than 48% effective against alpha and only about 30% effective against delta.

I'm a little confused as to what your point is? The vaccines are highly effective after two doses, but not very effective after only one dose.

I don't see 50% as "very little", but that's just semantics and not worth fussing over. I concede to you :)

Thank you for following up- I appreciate it.

50% (48%) is for Alpha (I'm actually a little surprised it's that low; IIRC it was a lot better in the initial studies, though those were on the ancestral variant, not Alpha). For Delta, it's 30%, per that article. I'd call that pretty low.

That said, other studies are available, and some have shown decent performance against Delta after one dose.

It’s unethical to gamble your citizenry on untested medical interventions regardless of outcome. There was enough time to sponsor a trial.

This is easy to say if one is living in the country with all the vaccine supply. Canada bought more doses per capita than any other country, yet US prohibitions on vaccine export meant Canada could not get enough supply in the first few months of the vaccine rollout. A calculated risk was taken to give first doses while waiting for supply to come online, which did eventually happen.

This was not some random experiment on the population. While the gold standard of a phase three trial was not available to support the longer interval, there was plenty of data about the performance of prior vaccines, and interim data about immunogenicity with a longer interval for the COVID-19 vaccines.

No. It is ethical to do that which maximizes life-saving outcomes. Saying that something is an "untested medical intervention" lacks the nuance of saying that some interventions are completely unknown, while others have fairly predictable and understandable effects.

The effects of a single dose were reasonably well understood as well as the impacts on transmission. Reducing transmission is a potentially more relevant goal than individual health outcomes in the grand scheme of things.

While I agree with you on the overall sentiment, it is very hard to apply sometimes. Here in Germany there were a lot of calls to start handing out Curevac doses. They had a few million ready to go, but we were still awaiting trial data.

Our government decided against the emergency usage in the end, and it was the right decision in hindsight, as it turns out that the vaccine is far less effective than its competitors, and could very well have had similar problems as AZ or Biontech.

The alternative could people taking their chances with covid. The do nothing option is not a neutral outcome.

Come on, we didn't even have time for the trials we actually ran. Thousands died while we waited for rubber stamps.

So was it ethical to gamble on a four week interval when it wasn’t proven to be the best option?

I still think that something else was unethical: not running challenge tests.

There were enough volunteers for them.

Gamble is the wrong word for this. It was a calculated risk as is everything in a pandemic or other evolving threat to public health.

No one ever claimed that it was the best option, just that it was the only option clinically tested. It would have been irresponsible to recommend a different option without at least some limited clinical trials. Sometimes you can't wait for perfect data.

After two doses, overall T cell levels were 1.6 times lower after the long compared with the short dosing schedule. However, after the longer dosing interval, a higher proportion of T cells present were ‘helper’ T cells, which are important for long-term immune memory and helping generate antibodies to prevent infection.

The data I'd like to see discovered is if and when this effect tapers off. Surely we need that to know the optimal time to take a booster? (This is assuming the vaccine makeup hadn't changed and you're not taking a booster to immunize against variants.)

> For the longer schedule, the antibody levels dropped off between first and second dose, which included the loss of any neutralising effect against the Delta variant. However, T cell responses were consistent, indicating they may contribute to important protection against Covid-19 during this time.

Does this suggest that ~8 weeks after the second dose one will still have protection from plain covid, but protection again Delta variants will be diminished?

The sentence you quoted refers to the period between first and second dose. My understanding is that "if you get exposed to the Delta variant on the day before the second dose, you won't have neutralizing antibodies".

It does not make a statement about what happens after the second dose.

Agreed, but it is suggestive that this is within the realm of possibilities, no? Otherwise, something interesting would have to be happening where after the first shot you lose delta ~immunity in eight weeks, but after the second you ~do not?

Possibilities sure, but IMO that doesn't translate to "likely". Other vaccines also give you only minimal or short protection after the first dose with long-lasting protection after the second (or third) one.

It is not a good study: "A total of 503 healthcare workers were recruited to the study, of which 223 (44%) had previously had Covid-19." The sample group is not representative of the population and with a large proportion already having had COVID, it is expected that the first dose of the vaccine acts like the second dose, and a second dose as a booster.

It is also ignoring the downsides of the longer gap, the main one being the increased likelihood of creating a vaccine resistant escape variant. The UK government admits that this is a risk: https://assets.publishing.service.gov.uk/government/uploads/...

"There is therefore an increased risk of virus replication under partial immunity after one dose than after two doses, so in the short- term, delaying the second dose would be expected to somewhat increase the probability of emergence of vaccine resistance - but probably from a low base."

Last time I looked, UK now had the 3rd highest case rate in the world. A variant factory you could call it.

Part of the justification of the risks of the increased gap was the high death rate at the time.

"Is such an increase material? It is not currently possible to quantify the probability of emergence of vaccine resistance as a result of the delayed second dose, but it is likely to be small. The UK currently has more than 1,000 COVID-19 related deaths each day and has limited supplies of vaccine. In the current UK circumstances the unquantifiable but likely small probability of the delayed second dose generating a vaccine escape mutant must be weighed against the measurable benefits of doubling the speed with which the most vulnerable can be given vaccine-induced protection."

That is no longer the case, vaccine supply is good and take-up is falling.

The Oxford AstraZeneca vaccine did have clinical trials with a longer gap as far as I understand, but Pfizer didn't. The mRNA vaccines have different properties but the UK government is treating all vaccines as the same.

Now with every small and pretty weak bit of evidence the government jumps on to justify their decision, which initially may have been the right choice but the unlocking and delta variant have changed the situation massively.

There was a similar study in Israel with some strong arguments against its findings: https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

And more good reading: http://www.thelancet.com/retrieve/pii/S0140673621004554

"We have no concerns regarding the second dose of AZD1222 at 12 weeks, as this is supported by evidence. However, if escape variants arise due to sub-optimal dosing with BNT162b2, they will likely be resistant to other vaccines that target the same viral spike protein. In conclusion, we would strongly recommend that the UK Government reverts to the two doses in a 3-week schedule (94% efficacy) for BNT162b2; or, as recently supported by WHO and the US Centers for Disease Control and Prevention, adopt no more than a 6-week delay to the second dose “in exceptional circumstances”."

I had mine three weeks apart, I wonder if I'll get different responses to the booster when it comes through (at this stage) next year.

One study of few people does not seem enough.

They started this longer interval, against manufacturers recommendation, supposedly because of stock and to give to more people, but kept the this longer interval even after the daily vaccination numbers dropped 10x

Now I'm glad I've waited 8 weeks !

Is it practical to ask people to wait 8 weeks? Will people be significantly less likely to show up to the second appointment after 8 weeks instead of 3 weeks?

In the UK the minimum wait is 8 weeks and there doesn't appear to be an issue with people failing to get 2nd doses.

I had my second dose in the UK after 5 weeks, by just going to a walk in centre and asking - apparently they had way too many doses they would be wasted otherwise, so they were happy to give it to anyone asking. Apparently the absolute NHS-mandated minimum is 3 weeks between doses, that's the one they can't disobey. But the 8 week minimum is much more flexible.

Until a few weeks ago the minimum wait was 12 weeks! Data on rates here: https://coronavirus.data.gov.uk/details/vaccinations

Looking at just the Cumulative data, ~79% of people in the UK that have taken the first dose have taken the second dose. Looks like it is practical. And that number doesn't account for people that haven't had their second appointment yet.

The wait period in British Columbia is about 7 weeks, and our #2 dose numbers look just as good as #1 (80% first dose, and 58% second dose, still averaging 60k doses a day)

The main risk I'd be worried about that people will engage in more risky behavior after the first but before the second dose.

It's a lot easier to hold out and skip some fun activities if there's a goal 4 (or rather 6) weeks ahead than if it's 8 (or rather 10) weeks.

That's about what it has been the whole time in my region and there's no sign of a problem yet.

That only matters to people who get vaccinated because they are afraid of COVID. I got my second dose ASAP, because I needed a certificate for travel, so I could go for well deserved vacation. I don't give a fuck about effectivness.

This sounds selfish, caring about your holiday not about infecting others, but the way it's written it also seems on purpose? I can't tell if this is flamebait. In case you're serious and don't find this selfish, what would be even better for (everyone's, and thus also yours) holidays would be no more pandemic. We'd get there with fewer extensions (mutations) if we have fewer hosts for it to breed resistance in. More immunity is more better as far as I know.

I'm also not fully on board with letting regulations or social things pressure you into doing a medical thing to your body for reasons other than because you believe it's the best option for your personal health. Not that I think you made a bad choice, it's probably also the best choice for your own health, but it should be a fully free and informed choice for everyone.

I suppose that, whatever the thought process and reasoning here, I'm happy you went with the option that benefits everyone. Keep it up and maybe one day you can't pretend to be a selfish person anymore :P (if that was, perhaps subconsciously idk, the goal here in the first place)

Not worried about long covid? Other article on HN suggests that even mild cases might cost you some IQ points

I have plenty of IQ points to spare. Also, I did get vaccinated, just didn't care about the few points of effectiveness I lose from a fast vaccination.

EDIT: also, what you claim is illogical: you say that even mild cases of COVID cause IQ loss, and yet no know vaccine protects against mild cases, best case scenario they turn severe cases into mild ones. So getting vaccinated is useless in that regard.

I mean, the Pfizer/Moderna vaccines still have between 90% and, let's say, 60% efficacy against mild cases, and the long covid severity scales with "how mild" your case is going to be.

There is a likelihood that Covid gives you so much brain fog that you'll have trouble continuing your high-IQ work, and vaccines reduce that likelihood.

If, due to the vaccine, you get a mild case or a case without any symptoms, perhaps all that happens is that your spatial reasoning is less speedy. And, as you say, you have plenty of that to spare.

So, it seems to me you should have quite some interest in vaccine efficacy across the severity scale.

It's your choice though, of course.

Man, the messaging around the vaccines is so damn frustrating. No wonder people are skeptical. “Get whatever is available when you are eligible” —> “Oh but not J&J unless you are over a certain age” —> “Or AZ unless over a certain age” —> “Don’t mix mRNA” —> “OK Mix mRNA if available. Just get fully vaxx’ed ASAP” —> “Just kidding, wait 8 weeks”

Like come on! I follow this reasonably closely and I am ready to storm the Ivory Tower over this messaging. I cannot imagine what someone who doesn’t follow this feels.

That's complex decision-making under conditions of uncertainty for you. The authorities themselves are partly to blame for not being totally clear that they're human and figuring this out on the fly like everyone else, but the general population is also to blame for acting like a bunch of spoiled children and feeling entitled to perfect answers and zero mistakes.

I'm in Australia, and our pandemic's management from some of our governments is a bit like dropped spaghetti. Ie it's a big mess.

Anyway, the frustrating issue is that advice seems to be risk based mixed with environmental conditions. Which seems sensible, but I actually think it's not the correct approach.

So right now we have a bloom of Delta in Sydney, and our medical advice was previously not recommending AZ because of the chance of blood clots. However now the situation is really quickly getting out of hand and they are recommending AZ.

It strongly seems like they considered Australia being some island all on it's own some massive mitigating factor which changed the impact of the virus. And as a consequence a lot of people are without any vaccine and a lot of hesitancy about AZ. The failure here was they thought they had time to wait for pfizer.

But Delta acts like Delta and is just spreading around like wildfire. I actually believe some of the advice is suffering from normalization of deviance. Where the deviance is being able to suppress the virus with things like quarantine. As opposed to getting everyone vaccinated.

Oh btw, I'm under 40 and got AZ because I'm willing to risk it. I've never been struck by lighting and i've done way riskier things.

Let's be honest. IMO the assumption of Australia being an island was right (as evidenced by the states that made sure their states were islands most notably WA). At this stage WA is clearly the "gold standard" of COVID management, not NSW. NSW, given the numbers it was taking through its "hotels" which never should of been permanent quarantine facilities in any case was not "an island" at all. They arguably were just lucky most of this time, and through hubris of the local people there this was considered good "gold standard" management.

The low tech easy solution for a country like Australia is really better quarantine facilities (i.e. not hotels in the middle of population centers) IMO coupled with a vaccine rollout geared to workers at the quarantine facility (and potentially freight facilities). Its easier to rollout the vaccine and subsequent updates to it for future variants to a smaller number quicker. States in Australia that limited their international intake seem to be doing better than particularly Sydney who were taking the most arrivals. It really isn't an island when your taking the brunt of international arrivals. The fact that it was even working (hotels) for as long as it did shows the effectiveness of a good quarantine strategy. Low tech, simple solutions usually trump high tech solutions that require everyone to participate (problem of the commons).

Admitting the uncertainty is my point. Instead they change the messaging week by week and act like this latest messaging is certain.

Each of those steps had more nuance being communicated than the half-sentence you summarize it with, often with intense public debate and different judgment calls from different health authorities. (AZ and if/how to use it is probably the biggest example, vaccination for children is another (at least here in DE that's a massive thing)) None of these things were "this is the absolute truth forever".

Exactly, people forget that actually, the official government message is NOT the snippet on BBC or in a newspaper, there's usually a much longer and complex explanation to be found directly on NHS website or you can ask your GP. I have this problem with my mum - she watches the news and complains that the government never explains anything properly - but I'm like, mum....you realize news stations aren't the government, right? You're just getting the abridged version and complain you don't see the full picture.

Often even just "read the newspaper article" vs just the headline or the TV news snippet.

The main message here is not "you have to/absolutely should wait 8 weeks". The main point is "countries that did stretch the schedule compared to what was in the initial studies probably didn't make a massive mistake by doing so" (EDIT: and of course it's a press release for a single study, not an official policy announcement)

Those are each reasonable things to say with certain conditions and caveats. I would guess the issue is with various experts and policy makers trying to simplify things "for" regular people. Different people have different priorities and different summaries.

Another issue is that some health officials won't recommend something until there has been an official study result. For example, it was very likely that mixing vaccine types would result in stronger immune responses. But almost no one was willing to recommend it until there was a study done. That's why Britain finally put together a tiny quick study just to get a result out that they could point to.

A related issue there is that the recommendations are all based on the quickest results to study. The short 3-4 week spacing was recommended only because testing longer gaps takes longer.

I don't get why you're downvoted - you are completely correct in your analysis of public perception!

The key issue underlying all of the chaos is that scientific literacy isn't taught much in schools. Too many people think that "once scientists have declared something, this may be as irrevocable as the stone platters on which Moses wrote the 10 Commandments", whereas the reality rather is that scientific knowledge is always expanding, including retractions or corrections as more data becomes available!

Another part of the problem is that politicians - not just in the US but also in the rest of the Western world - have dropped their role of taking in scientific knowledge and distilling reasonable policy out of it. And to top that, media has been massively cutting down on their "science journalism" departments that could provide context and education to public debate.

I mean, that's the nature of an emerging situation. What do you _expect_ health officials to do?

not OP but the alternative strategy is to start conservatively and then relax restrictions rather than pivoting between guidelines.

So in this case I think a more clearer solution would have been to be maximally cautious in the beginning, and then only when you're certain loosen what vaccines to apply when. The same way the British handed lockdowns. They started strict, only relaxed measures slowly, and made clear they won't reimpose stronger measures once lifted.

This is understandable to people because there is reassurance and clarity about how to proceed. Which is important because everything else destroys confidence.

But… what restrictions are you suggesting? There was one major restriction right from the start; many countries didn’t allow AZ for over 65s for a while, due to deficiencies in the first trial (and that one usually was dropped). But all other current restrictions are as a result of later discoveries.

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