[HN Gopher] Quarter-dose of Moderna Covid vaccine still rouses a...
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Quarter-dose of Moderna Covid vaccine still rouses a big immune
response
Author : _Microft
Score : 85 points
Date : 2021-07-10 19:12 UTC (3 hours ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| Animats wrote:
| _In the earliest trial of Moderna's mRNA-based vaccine, study
| participants received one of three dose levels: 25, 100 or 250
| micrograms. The top dose proved too toxic. The low dose elicited
| the weakest immune response. The middle dose seemed to offer the
| best balance: it triggered strong immunity and had acceptable
| side effects._
|
| That somewhat contradicts the article's claim.
|
| If you under-dose, there may have to be a booster shot. Then the
| whole inoculation program has to do the job twice.
| handmodel wrote:
| The difference is that in that trial they weren't looking at
| health outcomes. They were looking at people's blood and
| measuring antibodies.
|
| If it turns out that 25mg produces a small amount of antibodies
| - but that small amount is still more than enough to prevent
| the same number of hospitalizations that 100mg does - then it
| make sense to go with that.
|
| The dosage trials were only used to study the microbiology. Not
| the death/hospitalization outcomes.
| makomk wrote:
| The risk is that even if that lower dose with a lower
| antibody response works fine with existing variants, it might
| not fare so well against future mutations. I think this has
| already happened to a certain extent with the currently
| circulating variants - vaccination programs that gave worse
| antibody responses fared OK against the original variant, but
| not so well against newer ones.
| handmodel wrote:
| I think that is fair but I also find the status quo bias
| strange.
|
| If you think that variant changing is a bigger deal than
| getting them out fast what makes you so sure we shouldn't
| increase dosage another 50% or another booster?
|
| Right now it seems like the mRNA vaccines work fine and the
| variants are actually getting better at spreading but not
| killing.
| Zevis wrote:
| We don't need perfect immunity. Canada has shown that
| focusing on first doses over "full" immunity can work quite
| well at a population level.
|
| The flu vaccine is around 10-40% effective. Bu suddenly we
| pretend like if a vaccine doesn't give us 98% immunity,
| it's useless? Seriously?
| wccrawford wrote:
| I agree with what you're saying, and I noticed that trend
| earlier when people were talking about 70% vs 99%
| effective vaccines...
|
| But IMO, the flu vaccine is pretty useless. I've never
| had any confidence that it's actually doing anything for
| me or anyone I know. I notice no difference between years
| I get it and years I don't. And if the Covid vaccines
| were only providing 10-40% protection, this whole
| situation would be a _lot_ worse.
| saddlerustle wrote:
| 100% of the population with 70% immunity results in far fewer
| deaths than 25% of the population with 90% immunity
| belltaco wrote:
| I think that calculation will vary depending on age and at
| risk groups. If those 25% in the second option are older
| folks and/or obese/diabetic, deaths might be lower in that
| scenario.
| voidfunc wrote:
| 100% of the population is unrealistic tho. In the US were
| looking at realistically somewhere around 65-70%... stronger
| immunity is desirable here
| tbenst wrote:
| I think this makes great sense at the world population level. And
| after all, the Pfizer vaccine is only 30mg per dose, with
| equivalent (marginally higher) efficacy at preventing disease.
| The RNA sequences are highly similar as well, so I doubt that one
| expresses much more robustly. It's been long speculated that the
| moderna vaccine has more side effects with same efficacy due to
| the aggressive dosing, and reducing to 50mg or even 25 is
| supported by a plethora of reasonable data.
| Synaesthesia wrote:
| This is great news for Africa which really needs vaccines right
| now. It's great that all this vaccine research is going on. But
| the inequality of access is a huge problem.
|
| Up to now Africa hasnt had a big wave of covid, but this 3rd wave
| has hit us really hard (and I know, Africa is not a country, I
| live in South Africa).
|
| What experts warned about might happen is happening now: because
| of insufficient vaccinations the Covid pandemic will stick around
| and mutate in poor countries.
| afavour wrote:
| This is one of the things that depresses me the most... rich
| countries don't even need to be altruistic here. Be entirely
| selfish: send vaccines to worse off countries to cut down on
| the number of mutations that will inevitably arrive on your
| shores.
|
| The _really_ depressing part is that the exact same logic
| applies to climate change, so I'm not exactly full of hope for
| the future right now.
| makomk wrote:
| It doesn't matter whether your justification for why this
| should happen is altruism or selfishness, the same problem
| remains: a vaccination program of the scale and speed we've
| already seen is literally unprecedented, it's astounding that
| everyone managed this much, and yet even with that incredible
| effort there still aren't the doses to vaccinate the planet
| any time in the imminent future let alone the on-the-ground
| infrastructure to deliver them everywhere - and even the
| rich, developed countries with the best vaccine rollouts out
| there probably haven't reached herd immunity before new
| variants made that impractical or even impossible with the
| current vaccines.
|
| This isn't that remarkable. Previous attempts to deal with
| respiratory disease pandemics using vaccines have proved
| pretty futile, even though it is a standard part of pandemic
| planning.
| searealist wrote:
| mRNA vaccines have extreme cold storage requirements that
| make it very difficult to distribute to many places in the
| world.
| Synaesthesia wrote:
| It's not entirely impossible, I'm sure we would be fine
| with in in South Africa, and many African countries. Just
| need consistent power. But yes that is a hindrance.
| enaaem wrote:
| It is not a matter of not willing to share, but a capacity
| problem. All production is fully bought up. Throwing more
| money at it won't increase the supply.
| alsetmusic wrote:
| > It is not a matter of not willing to share, but a
| capacity problem. All production is fully bought up.
| Throwing more money at it won't increase the supply.
|
| This is why we should suspend IP / patent protection and
| increase production.
| prox wrote:
| That has already happened I think, but creating a new
| pipeline is hard.
|
| https://www.theguardian.com/world/2021/may/06/covid-
| vaccines...
| T-A wrote:
| Suspending IP protection does nothing to increase
| production capacity.
| jlmorton wrote:
| Moderna has said for over a year that anyone is free to
| use their IP. Intellectual property has precisely zero to
| do with production capacity.
| amluto wrote:
| There's IP and then there's IP. If Moderna published
| their complete protocols, cell lines, etc and allowed any
| qualified manufacturer to pay $5k/hr to consult with
| Moderna experts on how exactly to manufacture the
| vaccine, I wonder if there would be more supply.
| maxerickson wrote:
| What is stopping us from linearly scaling mRNA vaccine
| production?
|
| If throwing money at it won't help, there should be
| specific answers to that question.
| chitowneats wrote:
| The average age of death from covid is higher than the average
| life expectancy in the U.S.
|
| By and large Africa doesn't do mass testing the way the
| developed world does. No tests, no cases. Young population,
| very few deaths.
|
| Voila. No pandemic.
| andai wrote:
| Interesting perspective, I hadn't considered the age pyramid.
| The median age in Kenya is 20.
| chitowneats wrote:
| It's also not just the age pyramid.
|
| In covid deaths occurring in the under 65 population, there
| is often a significant comorbidity that contributed to
| severe illness. Obesity, diabetes, etc, are at the top of
| that list.
|
| Africa by and large does not have the same health profile
| or concerns as Japan, the UK, or the U.S.
|
| None of this is to suggest that vaccines should not be
| distributed there. I think they should.
|
| What I'm questioning is if COVID-19 deserves to be even on,
| let's say, the top 10 list of problems facing Africa in
| 2021. Probably not.
| NicoJuicy wrote:
| You're completely ignoring long covid.
|
| You don't need to die from COVID-19 to experience health
| issues, even without previous issues.
| chitowneats wrote:
| Do you have any links to peer reviewed evidence of "long
| covid"?
|
| I haven't seen anything remotely convincing. But I am
| open to changing my mind.
| comicjk wrote:
| This is a statistically shoddy talking point. The average of
| all causes of death is right at the average life expectancy,
| by definition. Any cause of death weighted towards the
| elderly will have an average age above the average life
| expectancy.
| chitowneats wrote:
| This is precisely my point. Quite easy to miss the spread
| of a virus when:
|
| 1) Your population is by and large not susceptible to
| severe illness from the virus. Rates of asymptomatic & mild
| cases are much higher than in developed countries.
| Tragically, this is because most do not live long enough to
| be in the high risk group.
|
| 2) No widespread testing. Pneumonia deaths are just
| pneumonia.
| [deleted]
| supergirl wrote:
| I was wondering if these companies put a much higher
| concentration to make sure the vaccine works. it was a race to be
| the first mass producer of vaccine, so I imagine a discussion
| like "the vaccine is probably effective with a dose of X, but
| let's do 2*X to be sure". or in other words, if the vaccine
| proves not effective, at least they know it's not because of a
| low concentration.
| nimish wrote:
| That's why they did the boosters too.
| handmodel wrote:
| A huge oversight was when it was approved for phrase III they
| should have run many (a dozen?) different trials at different
| dose amounts. It was already proven to be safe and nailing the
| dosing would have helped get shots into arms faster in the US
| and elsewhere.
|
| I'm on the extreme end of thinking it should have been approved
| faster - but even if you are a bit of a traditionalist I don't
| see how running concurrent trials on such an important
| potential vaccine wouldn't be a huge win.
| ebiester wrote:
| Tens of thousands were in this trial. How many hundreds of
| thousands of people should be sufficient to get it out the
| door?
| handmodel wrote:
| It would still only be the same number of people per trial.
| They wouldn't have gotten trouble finding volunteers.
|
| And even if they just prioritized starting the first one
| ASAP - they didn't do any dosage testing until after it had
| been released to general public for months. Even if not
| ideal they could have started dosage trials in November
| after all the data from the original was done. Instead,
| they waited six months before even considering this.
| belltaco wrote:
| Even if you find all those multiple number of volunteers,
| you still need additional vaccine doses to be
| manufactured, which can take longer because they need
| more supplies from third parties, and scale up early. Not
| to mention all the extra staff to run the trials.
|
| If somehow they're able to run trials on 12x the
| volunteers, I would rather that they increase the
| participants by 12x for the final dose so that you get
| more confidence in the Phase 3 study results and in
| finding rare side effects.
| Spooky23 wrote:
| You have to be cautious as we live in an era where anti
| vaccine beliefs are commonplace.
| loceng wrote:
| I'm curious what your knowledge or thoughts on potential non-
| vaccine treatments are like Ivernectin - and what you think
| of the response to them?
|
| Edit: ridiculous that HN community downvotes attempts to have
| conversation; you're part of the problem.
| Spooky23 wrote:
| Once manufacturing ramped I don't think vaccine quantities
| are an issue.
|
| Transport, preparation and process are very operationally
| challenging.
| belltaco wrote:
| It would be hard to recruit that many volunteers and staff to
| run a dozen trials, and reducing the study group size would
| mean less confidence in the results. Already we have seen
| blood clots and heart inflammation show up at rates that
| won't be caught even in larger scale trials.
| mahogany wrote:
| Finding the optimal dose is done in phase II, where various
| dose levels are tested on different groups of people. Phase
| III happens after the dose level is confirmed, and then you
| roll that out to tens of thousands of people. I think the
| main point of phase III is to test the final candidate, so
| you're not really experimenting with the formula at that
| point.
|
| If you check the papers for the mRNA vaccines, you can see
| that they did run several different dose levels and got
| pretty clear feedback that some were too high or too low,
| before moving on to phase III.
| handmodel wrote:
| I don't think this is accurate.
|
| If you read the abstract in phase II they gave it to a
| small amount of people and looked in detail how the immune
| system responded in these individuals. This is very
| granular data.
|
| Phase III is more like "We have no idea what the immune
| system did in certain people - but only 0.1% of vaccinated
| people ended up in hospital compared to 2% of placebo" or
| whatever.
|
| The important thing for the vaccine was too limit death and
| hospitalization. And phase II didn't tell us clear info on
| that.
|
| What if they had found that half the dosage ended up in the
| same number of hospitalizations? There's no way to get that
| from phase II data.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/
| mahogany wrote:
| Are you saying that my use of "clear feedback" isn't
| accurate? I mean this with respect to what was in scope
| for phase II, although I could see an argument against
| using that subjective language. Also, even more dosages
| were tested in phase I, again on a few number of people,
| but I'm not sure if that's different from how it's
| usually done.
|
| > The important thing for the vaccine was too limit death
| and hospitalization. And phase II didn't tell us clear
| info on that.
|
| Phase II is primarily to test that the "candidate is
| safe, sufficiently immunogenic, and maybe protective"[1].
| It's not clear to me that testing hospitalization
| percentage is in scope.
|
| [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/
| handmodel wrote:
| You said in your previous comment that phase II was about
| finding the "optimal dose" but that testing
| hospitalization data is not within the scope of phase II.
|
| In a very real-world sense the "optimal dose" is 100%
| about finding hospitalization/health data. The "optimal
| dose" in phase II is about the microbiology and isn't
| very precise in terms of how it translates to real world
| effects.
| tgsovlerkhgsel wrote:
| Or at least started running a second run of modified trials
| as soon as the phase 3 trials passed.
|
| The trials take something like 3 months from first shot to
| results, I think. It took a lot more than 3 months from phase
| 3 completed to most people vaccinated in most Western
| countries and obviously much longer in developing ones.
|
| But there is very little financial incentive to run such
| trials once you have a vaccine approved...
| handmodel wrote:
| 100%
|
| The problem is on the government side. They should have
| paid for this. It would have saved them money too - if it
| turned out they only needed to give out one shot of the
| mRNA doses or that they could cut down on dosage.
| msandford wrote:
| Back when this news hit
| (https://www.dailymail.co.uk/news/article-9033881/Half-dose-O...)
| I suspected that we might end up finding that ever smaller
| amounts of vaccine would be as effective as "full" doses.
| Obviously I didn't make any big public predictions of such since
| I'm a nobody but it's interesting to see it play out.
| bpeebles wrote:
| The current phase 2/3 trials Pfizer is doing for children under
| 12 is using a 1/3rd dose for 5-11 year olds and 1/10th dose for
| 6 months to 4 year olds, based on an earlier phase 1 trial.
| weaksauce wrote:
| to expand on this... while it is encouraging to see that there
| is a good immune system response to such a low level of the
| vaccine it's also true that in the real world for pfizer the
| two shot course is the only way to be really protected against
| the Delta variant.
|
| its use in places that don't have enough doses to go around
| would be huge though.
| msandford wrote:
| Does anyone yet know why only the pfizer two shot course is
| effective against the delta variant yet? Slightly different
| spike analog, different delivery, you just need huge
| efficacy?
| weaksauce wrote:
| from reddit...
|
| > the 30ug of genetic material in the Pfizer/BioNTech
| vaccine vs. closer to 100ug in Moderna's indicates to me
| that their RNA optimization was probably superior, and is
| likely part of the reason for the less severe side effects
|
| https://www.reddit.com/r/medicine/comments/kp1a00/moderna_v
| s...
|
| > Moderna probably used a higher dose than they needed to.
| This was discussed with the vaccine advisory committee.
| Apparently the dose they settled on for phase 3 trials was
| decided prior to having all the phase 2 data. They decided
| to error on the side of effectiveness when they picked the
| current dose. They basically admitted, if they knew then
| what they know now, they probably would have used a lower
| dose in phase 3.
|
| so basically 6 months ago they knew it was probably too
| much
|
| as to why the pfizer is effective against the delta it's
| probably just picking the right sequence that is slightly
| closer to the delta by chance.
| londons_explore wrote:
| It seems fairly likely to me that dividing the dose by 100 and
| giving it to 100 different individuals will have more benefit
| to the population than giving it to 1% of a population and
| leaving the other 99% unvaccinated.
|
| It's likely that had this strategy been done 6 months ago, a
| large number of dead people would be alive today.
|
| The only major downside is the population may come to believe
| the 'vaccine' is ineffective and not trust future vaccination
| efforts.
| amelius wrote:
| Is the required dose related to body weight?
| _Microft wrote:
| I bet we could optimize the dose depending on sex, weight, age
| or other factors (if we knew how it depended on them) but this
| is not how it is done. The dose is the same for all adults.
| acituan wrote:
| Not really, as the trials were done on representative samples
| of the general population, we know at least we are not
| underdosing anyone wrt those metrics.
|
| Reducing the dose as much as possible would be _minimizing_
| it.
| rossdavidh wrote:
| So, I think it's great that they're looking at this, and I even
| believe that on balance it is probably the best bet to go ahead
| with this idea in countries that have a vaccine shortage.
| However, I just have to point out:
|
| "Levels of both antibodies and T cells were comparable to those
| found in people who have recovered from COVID-19."
|
| I can think of another reason this might be true. Maybe, you
| know, most of these people actually got covid-19, in the months
| after their quarter-strength vaccination. Now, this might still
| indicate that it helped them out, since they apparently were
| asymptomatic or at least did not have a serious enough case to
| attract the attention of the researchers, but it would not help
| stop the spread of the virus. So, the idea that there is no
| downside or risk to going with the quarter-dose, is not
| necessarily true. It could be that a quarter-dose leaves you just
| as likely to get (and perhaps spread) the virus, although it does
| prevent death or serious hospitalization.
|
| Again, I think on balance it's worth the risk, given the
| situation many countries are in, but I just think it should be
| acknowledged that it is still a risk.
| mrtesthah wrote:
| > Maybe, you know, most of these people actually got covid-19,
| in the months after their quarter-strength vaccination.
|
| No need to speculate. This is easily disproven simply by
| checking for antibodies against the viral capsid and other non-
| RBD proteins. Those antibodies would not be present in someone
| unless they were actually infected.
| johnchristopher wrote:
| What about Pfizer vaccine ? Are both Moderna and Pfizer close
| enough to speculate same results ?
| lvs wrote:
| The Pfizer vaccine's mRNA dose is already about 1/3 of
| Moderna's.
| HeavenFox wrote:
| A dose of Moderna has significantly more genetic material than
| a Pfizer one to begin with.
| _Microft wrote:
| Yes, this is in the works: "A study in Belgium is comparing a
| lower-dose version of the vaccine from Pfizer-BioNTech against
| the standard dose."
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