[HN Gopher] Half Doses of Moderna Vaccine Produce Neutralizing A...
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Half Doses of Moderna Vaccine Produce Neutralizing Antibodies
Author : elsewhen
Score : 88 points
Date : 2021-02-14 18:29 UTC (4 hours ago)
(HTM) web link (marginalrevolution.com)
(TXT) w3m dump (marginalrevolution.com)
| vmception wrote:
| Which retail job can I get to bump me up the list on vaccination,
| but doesn't actually increase my exposure possibility?
|
| I would just stick with trying to follow rumors of thawed
| vaccines about to be thrown out for the day, but all of my group
| chats are jetsetters and they're often easily swayed by
| conspiracies or are _just_ Republican and I don 't have energy to
| ask about being vaccinated there.
|
| edit: well its nice that I was able to crowdsource a discussion
| here! as you see, the energy of doing this in a sequential chat
| is much greater than a nested thread chat. really great insight
| into how to get it, thanks lifehackernews!
| elric wrote:
| What makes you think that you are somehow entitled to faster
| vaccination?
| sneak wrote:
| There is an argument that the rationing/prioritization scheme
| that is currently in use is inherently unjust, and that _no
| one_ is entitled to faster vaccination than anyone else.
| Spooky23 wrote:
| That's a consumer argument. The public health argument
| while vaccination is still constrained is that you
| prioritize vaccination for populations where they are most
| likely to be hospitalized.
|
| What we've seen is that if hospitals aren't overloaded,
| they are effectively able to treat people.
|
| In a few weeks, as production ramps, the priority will
| shift to mass vaccination to everyone. You'll literally
| have vans driving around setting up pop up events.
| owenmarshall wrote:
| What is the argument against prioritizing those who are at
| significantly higher risk of death?
| doteka wrote:
| I'll bite. There is actually a very simple argument to be
| made as long as you accept the premise that 1. Death is a
| natural part of life, and 2. It's not years of life that
| should be saved, but _quality_ years of life.
|
| I find it unethical to take away all quality of life for
| hundreds of millions of young people in the prime of
| their lives, as well as destroying thousands of small
| businesses, so that bed ridden 90 year olds can be bed
| ridden for a couple more years, at best. Yet this is
| exactly what is happening, at least in Europe, with
| draconian lockdowns and curfews in place while
| vaccinating groups that didn't leave their houses pre-
| COVID either.
|
| With how things are going currently in my country my
| peers and I will be lucky if we can be vaccinated in
| 2021.
| owenmarshall wrote:
| If we are going all in on "project cull the old", we're
| missing a few big things.
|
| One that jumps out is a blanket, age-based DNR. A 70 year
| old who has been refused the shot but subsequently
| develops Covid is significantly more likely to be
| hospitalized than your "prime of their life young
| person", for whom Covid isn't nearly as likely to be
| severe.
|
| This means they're going to be an overall resource strain
| on the system. It wouldn't be logical to refuse
| vaccinations for those most likely to be seriously
| sickened by the disease _but then_ to try to provide
| advanced life support when they need it.
|
| We will need to convert some percentage of hospital staff
| into "Covid hospice workers" to allow those who are sick
| to die as peacefully as one can when their lungs are
| shutting down.
| doteka wrote:
| I get that. I don't think you get my point though. The
| reason I want young people to get vaccinated is not due
| to COVID, since they're very unlikely to have severe
| complications anyway. In fact, the actual vaccination is
| not the point at all.
|
| The reason I'd like them to be vaccinated is so that
| normal life can resume to some degree. All public places
| save for grocery stores and pharmacies have been closed
| here since early December. There's been a 9PM curfew in
| place for a month with no end in sight. People's mental
| health is rapidly deteriorating. I would not be making
| this argument if we were simply required to wear masks
| and could go about our business as is the situation in
| many places around the world. But that is not the case at
| all here.
| vmception wrote:
| That's kind of why I want the vaccine early, because
| there are a lot of underground things that are happening
| _anyway_ that I 'm avoiding. When I could be having fun.
|
| I don't think just _swapping_ priority from elderly to
| prime age is a solution. As elderly will still be the
| ones bogging down emergency services, making relatively
| benign injuries a huge massive problem for everyone else.
| When returning to the normal distribution of emergencies
| after opening everything up, this is still a disaster for
| the hospitals.
| fastball wrote:
| This isn't my stance, but I'll steelman it anyway:
|
| Those at highest risk of death are the 70+.
| Coincidentally, people 70+ also have already led long
| lives / have the least utility left to give back to the
| society that is doing the prioritization. It is therefore
| more important to give doses to young people first, as
| someone needlessly dying with 60 years left on their
| clock is significantly worse than someone who has already
| had the opportunity to live a full life and statistically
| would've died within the next 10 years anyway.
| toomuchtodo wrote:
| Doses that go to waste because the prioritization system
| ignores logistics. Utilization should be optimized for.
| MaxBarraclough wrote:
| Seems like a false dichotomy. You can have a policy of
| prioritisation while also allowing vaccination of non-
| prioritised people if/when there are excess doses
| available that are approaching expiration. This is the
| approach currently being taken here in the UK.
|
| https://www.bbc.co.uk/news/world-55841017
| owenmarshall wrote:
| The "all or nothing" approach many states has built is
| extremely foolish, yes, but that isn't inherently part of
| an approach based on prioritization.
|
| You can prioritize for the sickest while simultaneously
| optimizing for all doses being used.
| toomuchtodo wrote:
| (Removed redundant commentary, leaving citations)
|
| https://thehill.com/policy/healthcare/533364-fda-chief-
| urges... ("FDA chief urges states to allow COVID-19
| vaccinations of lower-priority groups")
|
| https://www.nbcnews.com/news/us-news/thousands-
| covid-19-vacc... ("Thousands of Covid-19 vaccines wind up
| in the garbage because of fed, state guidelines")
|
| https://www.npr.org/2021/01/28/961722489/why-are-health-
| care... ("They're A Precious Commodity, So Why Are Some
| COVID-19 Vaccines Going To Waste?")
|
| https://www.propublica.org/article/covid-vaccine-wastage
| ("How Many Vaccine Shots Go to Waste? Several States
| Aren't Counting.")
|
| https://www.medpagetoday.com/special-
| reports/exclusives/9093... ("There are vaccines that are
| being wasted and that is a travesty," Terry Fulmer,
| president of the John A. Hartford Foundation, told ABC
| News. "Even one dose wasted is too many.")
| owenmarshall wrote:
| > The "all or nothing" approach many states has built is
| extremely foolish, yes, but that isn't inherently part of
| an approach based on prioritization.
|
| You're agreeing with me.
| sneak wrote:
| What is the argument _for_ it that entitles anyone to cut
| the line?
| owenmarshall wrote:
| If you start from the assumption that a successful Covid
| vaccination rollout protects the most people from serious
| illness and death, it follows pretty quickly. My parents
| are significantly more likely than I am to be
| hospitalized and/or die from Covid than I am. My
| grandparents as well, but their risk is even an order of
| magnitude higher than my parents face.[1]
|
| A successful vaccination program, then, would
| aggressively work through the most vulnerable populations
| first.
|
| [1]: https://www.cdc.gov/coronavirus/2019-ncov/covid-
| data/investi...
| sneak wrote:
| Yes, that seems to be the consensus, although I don't
| share it.
|
| I was answering the question posed by someone asking why
| someone felt entitled to faster vaccination.
| owenmarshall wrote:
| > Yes, that seems to be the consensus, although I don't
| share it.
|
| I know, you said:
|
| >> There is an argument that the rationing/prioritization
| scheme that is currently in use is inherently unjust, and
| that no one is entitled to faster vaccination than anyone
| else.
|
| I'm curious what that argument is.
| [deleted]
| kmeisthax wrote:
| Yes; however, prioritization lets us speed up the effects
| of population-scale vaccination by either...
|
| 1. Vaccinating people who are the most likely to get sick
|
| 2. Vaccinating people who are the most likely to spread the
| virus
|
| Option 1 makes the death and hospitalization rates fall
| quicker, so that anyone we miss is more likely to still
| have a hospital bed to get treated in. Option 2 reduces the
| total number of people exposed to the virus.
|
| The whole point of vaccination is to keep people from
| having to go to the hospital or dying - protecting the
| weakest first achieves that better than random
| vaccinations. Someone like me who basically lives in his
| room and works remotely can afford to wait for shots -
| someone who works in retail and has 1000s of exposures per
| day needs their shots yesterday.
| gxx wrote:
| Vaccine trials have shown that approved vaccines reduce
| moderate to severe illness and death. There is no trial-
| based evidence that they prevent people from catching the
| virus and spreading it [1]. It's even possible that
| people who are vaccinated are more likely to be
| asymptomatic and more likely to unknowingly pass it on.
|
| So "vaccinating people who are the most likely to get
| sick" is the only option supported by the evidence. Or
| preferably vaccinate people most likely to become
| moderately to severey ill, or die.
|
| At this time we should not be "vaccinating people who are
| the most likely to spread the virus". We don't know if
| approved vaccines will help with this.
|
| [1] https://www.bbc.com/future/article/20210203-why-
| vaccinated-p...
| gfodor wrote:
| It's arguable the point of the vaccine is secondarily
| about protecting individuals due to the immunity it
| confers, and primarily about accelerating herd immunity
| to kill the virus off, which would counterfactually save
| thousands of lives per day in perpetuity. (It's in either
| case very close between the two.) Given this, it makes
| prioritization pretty tricky under a supply constraint
| after you've immunized people who are objectively in a
| revere risk pool. For example, if we knew someone would
| be a super spreader, but would be at a low risk of severe
| covid, the margin of lives saved by prioritizing them
| over others that are at more risk of severe covid may be
| much higher. (Fwiw, I am skeptical the current
| prioritization regimes are designed around this
| optimization problem.)
| sneak wrote:
| > _Someone like me who basically lives in his room and
| works remotely can afford to wait for shots - someone who
| works in retail and has 1000s of exposures per day needs
| their shots yesterday._
|
| I think this is an oversimplification. We are living in
| our rooms because we choose to; many who don't work in
| retail that _could_ be living in their rooms are not, and
| are voluntarily engaging in 1000s of exposures per day.
| If those people are young and not in healthcare (mostly
| true), such potential superspreaders are not priorities
| for vaccination due to this convoluted priority system.
| MattGaiser wrote:
| I interpreted his question as how to become entitled to it
| more quickly.
| TameAntelope wrote:
| It's a generous interpretation, but using prioritization to
| determine how best to help feels at least roughly accurate.
| We are, as a society right now, being pretty explicit about
| who we think is most valuable.
| johnchristopher wrote:
| How else could it be interpreted?
| TameAntelope wrote:
| Oh, I guess they could have meant as a way to pretend to
| be more valuable than they intended on being.
|
| Signing up as a rideshare driver but offering no real
| rides, for example.
| johnchristopher wrote:
| > Which retail job can I get to bump me up the list on
| vaccination, but doesn't actually increase my exposure
| possibility?
|
| Clearly the objective is getting the vaccine and not
| doing something for the greater good.
| vmception wrote:
| why don't you think those are mutually inclusive?
|
| there exists retail [essential worker] jobs that don't
| currently expose you to alot of people
|
| and would fit the categorizations created by the state
|
| the same goes for health care professionals or education
| workers
|
| surprising to see how much the consensus here is
| grasping. newsflash remote tech workers, you dont have to
| keep the same job or only one job and your circumstance
| may not actually be privileged
| johnchristopher wrote:
| > why don't you think those are mutually inclusive?
|
| Because the question is not "Which retail job can I get
| to help things going on, but doesn't actually increase my
| exposure possibility?".
|
| It seems to me the motivation is only getting the
| vaccine, OP doesn't mention the will/objective to help.
|
| OP didn't say "I want to help retail, how do I do it
| without getting exposed ?" ?
|
| His objective is to get bumped on the vaccine list by
| going retail with the least exposure. That's literally
| his statement.
| vmception wrote:
| sounds like you're more triggered by the brevity of the
| statement which has already been clarified for you, by
| me, OP
| vmception wrote:
| OP here, thats an odd interpretation
|
| The plan is to actually have the job and its duties and
| fit in the classification. I dont want it to be
| counterproductive if I can also just wait. So there
| exists some essential worker jobs that dont really
| include being surrounded by aerosol spores all day.
| TameAntelope wrote:
| I was asked what other interpretations could be and
| provided one. I wasn't suggesting this was your
| intention, in fact I explained how it probably wasn't in
| my comment directly prior.
| toomuchtodo wrote:
| I have heard signing up as a rideshare driver if your state is
| prioritizing them as essential workers has worked.
| vmception wrote:
| I've been thinking about outdoor valet driver in hospitality
| sector, at a hotel.
|
| I'll look into the ride share thing I hadn't considered
| scouring each states "what is an essential worker" list. Or
| as another person wrote: writing bots to check some
| appointment list.
| throwaway189262 wrote:
| Lol wish I had any jetsetters in my social circles. I would
| probably have a lot more money.
|
| Anyways, how I did it was have a pre existing condition and act
| like a scalper. Appointments get taken within seconds of
| opening up, I assume many are writing their own bots.
|
| I wrote something to notify me when a slot opened up and
| clicked links many times over a period of a week until a
| managed to get a spot.
|
| I am in group 1B which is getting vaccinated here so I didn't
| feel it was unethical.
|
| If you don't have a pre existing conditions that raises your
| risk (and you're rich) I suppose you could look up the US
| territories and zip codes with highest adminstration rates and
| travel there. Some are approaching 35% so they will be opening
| general doses for anyone soon
| vmception wrote:
| > I suppose you could look up the US territories and zip
| codes with highest adminstration rates and travel there
|
| yeah by default I'm very low on the list if I dont get crafty
|
| I could do that, I already travelled to a low covid area and
| quarantined and didnt bring it with me
|
| I met some ppl that got it through their tribe, so I
| contacted mine across the country but in that state they
| arent doing anything for indigenous.
|
| Its a little weird how vaccines are aiming to be apportioned
| across all states at the same time. When really there is some
| lower hanging fruit than others. Like in one week you can
| send a freezer full to Wyoming or Hawaii and be done with
| those states, and only have temporarily reduced a 6 million
| allocation for California by 2 million!
| snissn wrote:
| Not sure how formal they are at checking employment or pre
| existing conditions.. Would depend state by state
| ingenium wrote:
| Pennsylvania (at least at the pharmacies) doesn't verify
| anything. It's all self certification. You say that you
| qualify for 1A to make the appointment, and they don't ask
| you anything when you show up. But Pennsylvania's criteria
| for 1A is pretty broad, potentially representing 40-60% of
| the population. So tons of people qualify, but appointments
| are really hard to come by.
| vmception wrote:
| Hadn't considered that, I'm just watching every state mess up
| their own "phases" and dissatisfied at the federal
| apportioning
|
| I can get a job, at least then I wouldn't be pretending that
| "we're all in this together" right?
| henrikschroder wrote:
| The risk of dying for the 70+ crowd is significant and much,
| much higher than for regular influenza. The risk of dying for
| the below 50 crowd is negligible and on par with regular
| influenza.
|
| Prioritizing the elderly _literally_ saves lives.
|
| Jumping the queue if you belong to a group that is not at risk
| is incredibly selfish and immoral. You can wait a couple of
| months, it won't kill you.
| fastball wrote:
| Morality is not as objective as you're making it out to be.
|
| If a 70+ that otherwise would not have died from COVID gets
| vaccinated but on account of not getting vaccinated the OC
| dies from COVID, is that moral?
|
| Utilitarian maximalism (via statistical predictions) is _an_
| approach to morality, not _the_ approach.
| fra wrote:
| Go ahead, find an approach to morality that leads to a
| healthy 30yo getting vaccinated while a 70+ does not. I'll
| wait.
|
| The length to which people with no morals will go to
| convince themselves they are good never ceases to amaze me.
| [deleted]
| sgc wrote:
| Only if they will save more lives by being vaccinated
| than if the 70 year old was. We should be focusing on
| people who are higher risk of being transmission vectors,
| such as grocery store employees etc, at the same time as
| vaccinating the weak.
| fra wrote:
| Again if the OC was a frontline worker we wouldn't be
| having this conversation.
| s1artibartfast wrote:
| If the 30 yo works at a nursing home for the elderly
| while the 70 yo lives alone in a cabin in the woods
| fra wrote:
| If the OC was working in a nursing home, we wouldn't be
| having this conversation...
| dragonwriter wrote:
| > Go ahead, find an approach to morality that leads to a
| healthy 30yo getting vaccinated while a 70+ does not
|
| If the 30 year old is employed in a position with many
| unavoidable close contacts, the expected number of lives,
| life-years, or QALYs saved by vaccinating them can be
| much higher than the 70 year old, if the latter has few
| unavoidable close contacts.
| aviraldg wrote:
| Why are we trying to maximize human lives saved as
| opposed to human life-years saved?
| fra wrote:
| You're an idiot. Vaccinating 70+ yo maximizes both.
| imwillofficial wrote:
| Is name calling against HM rules?
| henrikschroder wrote:
| Generously assuming people live to 90, saving a 30yo who
| would have died of covid saves 60 life-years, while
| saving a 70yo saves 20 life-years, i.e. 3x more.
|
| But the risk of dying is around 50x higher[1] for a 70yo
| compared to a 30y, which means you have to vaccinate ~15x
| as many 30yos as 70yos to save the same amount of life-
| years.
|
| So vaccinating the elderly first both saves lives _and_
| more life-years.
|
| [1] https://www.cdc.gov/coronavirus/2019-ncov/covid-
| data/investi...
| dragonwriter wrote:
| > Generously assuming people live to 90, saving a 30yo
| who would have died of covid saves 60 life-years, while
| saving a 70yo saves 20 life-years, i.e. 3x more.
|
| This makes the fallacious assumption that if life
| expectance at age X is n years, life expectancy at age
| X+k is n-k years.
|
| This is very much not true. See, e.g.,
| https://www.ssa.gov/oact/STATS/table4c6.html
|
| Using actual life expectancy by age makes the number of
| life years saved at age 70 much closer to that at age 30.
| s1artibartfast wrote:
| Overall good point. Much closer but still significantly
| different. The life expectancy is 14 years vs 48
| gfodor wrote:
| Of course with a highly transmissible virus the opportunity
| cost between vaccinating an isolated 70+ person and a young
| person who comes in contact with many 70+ people is tricky to
| ascertain. That said, I don't think here in CA the tiering
| system is attempting to minimize deaths by accounting for
| expected transmissions.
| vmception wrote:
| Getting a retail job or getting a thawed vaccine about to be
| thrown out does neither of those things
|
| Save that copypasta for something you understand
|
| The state handles the prioritization and they already
| prioritize the elderly. When their infrastructure fails at
| making appointments, a vaccine dose will be destroyed so
| there is greater utility for someone outside of the queue to
| use it at that point
| bagacrap wrote:
| I know people who are in their 30s with no pre existing
| conditions who have already been vaccinated because:
|
| * they work for a hospital system (in IT) * they work at a
| university (doing research) * their family member has a pre
| existing condition (but somehow that family member is not the
| only one to get a vaccine)
|
| In addition to this, smokers and those /who have already
| recovered from covid/ are lined up to get first /and second/
| doses before I get a single dose. I think it's fair to think
| of the system the politicians have decided on as flawed; to
| use your rhetoric, it literally ends lives to waste 2 doses
| on those who have already recovered from the illness. If gp
| wishes to apply his own sense of rationality to the process,
| I don't blame him.
| henrikschroder wrote:
| I agree that the priority system is screwed up in many
| places and that as a result a lot of people were vaccinated
| who really shouldn't have been at this stage.
|
| But that's the moral choice of the people who designed
| those systems, and the people who didn't decline even
| though that was the right choice.
|
| But two wrongs don't make a right. It's still wrong for you
| to jump the queue, regardless of what everyone else is
| doing.
| clairity wrote:
| > "Prioritizing the elderly _literally_ saves lives."
|
| that's true, but a bit naive. the utility function shouldn't
| simply be a function of age, as that would ignore important
| other factors, like transmissibility, that affect overall
| population-level outcomes. QALYs[0], while not impervious to
| critique, would be a better target for maximization.
|
| but the problem with that, again, is political, not
| technological or even psycho-social. that prioritization
| metric would be perceived as too complicated (harder for most
| politicians to explain without potentially exposing their own
| ignorance), but moreover, doesn't serve the interests of the
| largest political donors.
|
| [0] https://en.wikipedia.org/wiki/Quality-adjusted_life_year
| henrikschroder wrote:
| Do the napkin-math calculation of QALYs saved per
| vaccinated 30yo compared to 70yos.
|
| Hint: The IFR difference between a 30yo and a 70yo is _at
| least_ 50x.
| throwaway189262 wrote:
| This is less clear-cut than it seems because nearly everyone
| that's highest risk is retired and doesn't really need to
| leave the house. Is it better to tell a dozen pensioners that
| leave the house once a week for grocies to stay home so
| younger people can get vaccinated and go back to work?
| Possibly, depending on who you're asking.
|
| Younger people are far more mobile and so contribute greatly
| to the spread of the virus. The old and sick don't go out
| much so aren't the ones spreading the virus.
|
| Is it more important to stop the spread as quickly as
| possible or directly vaccine the more vulnerable? It's hard
| to know, and it probably depends on how much vaccine you
| have. Countries like the US with lots of vaccine may be
| better off vaccinating the most mobile members of society
| first to drop total infections ASAP. Countries with less are
| better off focusing on the vulnerable because they're a long
| way from herd immunity.
|
| If you have enough vaccine supply you will minimize deaths by
| eliminating transmission quickest which implies vaccinating
| the most exposed, not the most vulnerable.
| imwillofficial wrote:
| Throwing more variables at a question we already have an
| answer to is a waste of time. We know that older people get
| it more, die more, and are more at risk under all
| circumstances.
| throwaway189262 wrote:
| Less of them may die if we can get R0 under 1.0 faster by
| vaccinating those spreading the virus. It's absolutely
| still an open question IMO.
|
| You are wrong about the first part. There are way more
| under 65 infected than over. And I've seen some
| preliminary studies that they do 80%+ of the viral
| spreading.
| henrikschroder wrote:
| It is also infinitely easier to find old people than it
| is to find uninfected super-spreaders, we'll have
| vaccinated all the elderly long before anyone could
| develop a system to find the biggest potential spreaders.
|
| Also, with vaccine production ramping up, a lot of
| countries project that they'll have vaccinated everyone
| by summer. Who cares if there's a better model? Elderly +
| frontline healthcare workers is a _good enough_ model, go
| go go!
| russholmes wrote:
| I have seen this stated before. What is your source please?
| This is false: SARS-CoV-2 is significantly more lethal than
| seasonal influenza for all ages past puberty. In fact, at 50
| it is almost 15 times more lethal.
| https://github.com/mbevand/covid19-age-stratified-ifr
| henrikschroder wrote:
| If you are below 50, risk factors play a significant role
| in determining your actual IFR, while if you're above 70,
| your age is the primary risk factor.
|
| I don't think your graph adjusts for that, and I think the
| difference in IFR between covid and the flu for _healthy_
| people under 50 is smaller. We 're already at pretty small
| risks for those ages, and even if the difference is still
| 10x, it is - to use a highly scientific term - whatevs.
|
| So if you are _healthy_ and under 50, you won 't die from
| covid, and you shouldn't jump the queue. Better?
| Montika wrote:
| okay
| throwaway189262 wrote:
| If you read the trial data this is a foregone conclusion. The
| Moderna vaccine produces antibody titres over twice as high as an
| actual infection from the data I've seen.
|
| My theory is that these companies knew they only had one chance
| to make a working vaccine, so they did everything they could to
| make it not fail. Double doses, 5x what was needed in monkeys,
| gold standard adjuvants.
|
| I would not be amazed in the slightest if they decide to half-
| dose the vaccine or do away with the second shot or even both.
| They probably didn't have time to run the trial any other way
| Etheryte wrote:
| There is a conceptual misunderstanding here. Raising the dose
| doesn't mean you have a higher efficacy, in fact it can just as
| easily have the reverse effect. Vaccines aren't beer where you
| consume twice as much and get twice as drunk.
| IgorPartola wrote:
| Granted. But there is a minimum dose necessary to produce
| antibodies. If you are in a situation where you are guessing
| completely blindly (because no trial like yours has been done
| before), do you worry more about falling below the minimum
| required dose or above the maximum dose past which you get
| diminishing returns or even lower efficacy? I think it's
| reasonable to worry more about the minimum dose because you
| can always half the doses later. Finding out at the end of a
| multi-month trial that you didn't give enough in your doses
| would be a big setback. Just look at what happened with
| Assyria Zeneca when they started mixing up dosing in their
| phase III. They were the most promising vaccine last summer
| and they haven't even concluded their US phase III trial yet
| as a result.
| throwaway189262 wrote:
| I mean technically an alcohol could exist that makes you less
| drunk after twice as much but how likely is that? IMO about
| as likely as a vaccine that produces less immunity with
| higher dosage
| CyanLite2 wrote:
| If you look at some of their published Phase 2 data, they were
| actually getting good responses from their 25mcg dosing. But
| you're correct--this was the fastest vaccine development in the
| history of mankind, and they errored on doing the 100mcg
| version just to make sure the efficacy was high enough because
| they didn't have time to test it on a wider population or do
| challenge trials.
|
| Imagine the blowback on mRNA vaccines in general if they went
| with the low-dose version and got lowered efficacy...
| throwaway189262 wrote:
| Yup agree 100%. I thought I saw some pre-trial data on 10mcg
| in monkeys and even that was somewhat effective.
| Slartie wrote:
| There's no adjuvants being used at all with mRNA vaccines.
|
| Also, there were smaller sub-trials done with just one shot,
| and those showed significantly weaker immunization, although
| telling exactly how much weaker is hard due to little data
| available and thus very large margins of error.
| throwaway189262 wrote:
| No traditional adjuvants is interesting, but I know the RNA
| is modified. It's not the exact mRNA spike protein. I believe
| they modify the amino acids to modulate immune reaction which
| may accomplish the same thing.
|
| The immune system doesn't like non-human RNA. Certain
| sequences, or even abundance of certain amino acids out of
| balance with human codes can set it off. Special RNA coding
| may be used in place of traditional adjuvants but much of it
| is proprietary at this point
| jhayward wrote:
| The lipid nanoparticles that the mRNA is bonded to play a
| dual role, enabling the mRNA to traverse the cell boundary,
| and also as an adjuvant.
| BurningFrog wrote:
| They also picked very short booster dose times (3 or 4 weeks)
| to get study results quicker.
|
| Usually you have a longer pause, which gives somewhat better
| results.
|
| Now those numbers are treated as sacred by so many.
| throwaway189262 wrote:
| It is unfortunate. You can't even avoid downvotes in a fairly
| rational place like HN :) .
|
| I've been following the vaccine development pretty closely
| and everything looks like a "this can't fail" mentality.
|
| People need to realize that it's rational to ask if we really
| need the dose this high and really need a booster because if
| we find out we don't, it could double or even quadruple our
| vaccine supply. That could save half a million lives.
|
| It's good to ask questions like this especially when there's
| a massive worldwide vaccine shortage
| faitswulff wrote:
| I wonder if they, like Pfizer, will take the opportunity to
| declare that they have shipped 2x as many doses retroactively (in
| Pfizer's case it was an extra dose in every vial).
| xiphias2 wrote:
| Hundreds of millions of people would pay 5x the current price
| to get the vaccine faster. I feel like the policy of
| governments getting a monopoly on vaccine distribution is
| stopping companies in competing for speed of vaccine production
| and building more factories.
| ornornor wrote:
| I don't want to live in your world.
| epistasis wrote:
| No, that's preposterous, paying 5x more won't increase
| production capacity any more.
|
| There's already massive incentive to ship first, since there
| are competing vaccines. If an additional $10B-$100B could
| result in additional production of mRNA vaccine, it would
| have been delivered by governments if not by investors.
|
| This is simply a new tech with new techniques. Throwing extra
| money at a problem when there isn't a chance of increasing
| production capacity only causes inflation of prices, and
| rentierism. There is no benefit.
| feral wrote:
| It's a huge claim to say that $100B extra couldn't have
| resulted in a speed up.
|
| What makes you so sure of that? What's the manufacturing
| bottleneck that an extra $100B up front couldn't
| parallelize?
|
| I just have trouble believing that without some evidence?
| epistasis wrote:
| It's a far more remarkable claim that $100B _would_
| improve production capacity, since that 's a tiny tiny
| fraction of the costs of delay.
|
| But if you think that producers are intentionally holding
| back, and don't understand mRNA vaccine differences from
| adenovirus vaccines that have been used forever, this
| might help:
|
| https://blogs.sciencemag.org/pipeline/archives/2021/02/02
| /my...
| BurningFrog wrote:
| For mRNA vaccines, this is the first time they've ever
| been produced at all, and it's for the biggest
| vaccination campaign in history.
|
| So I can see how that can't go much faster.
|
| For regular tech vaccines, you're probably right.
| feral wrote:
| OK, but conversely there were literally no mRNA vaccines
| mass produced a year ago, and now they are delivering
| hundreds of millions of doses this year - so they've
| clearly being able to scale production quite quickly.
|
| Its a big claim to say another $100B wouldn't have scaled
| it faster. I'm sure they still have bottlenecks, and
| financial risks they weren't willing to take.
|
| $100B is a lot of resources - but a justified amount
| given the economic costs, which is the point.
| dependsontheq wrote:
| A tech comparison would be 4 or maybe 3 nm chips. Imagine
| everybody in the world would fork over 200B and order 7
| billion chips this year... your constraint in that case
| is the manufacturing equipment and there are only so many
| experts in that area. The vaccine technologies we are
| using are scaled for the first time so you don't have a
| big pool of experts or companies. The Chinese vaccine is
| probably the one best suited for scaling up and they are
| doing that rapidly.
| tchalla wrote:
| And some of other hundreds of millions won't be able to pay
| for vaccine. Are you sure you want to decide on health
| outcomes based on income / wealth?
| xiphias2 wrote:
| The cost is in ramping up production, actually after it is
| ramped up, it's generally cheaper to produce an additional
| vaccine (Wright's law). With the current pace people in
| most countries need to wear masks for years to come.
| owenmarshall wrote:
| I mean, _gestures at health outcomes in America_ , we do
| that today.
| mhh__ wrote:
| If this were purely a logistics problem then I would sort of
| agree with this, at least in the sense of being an avenue
| worth trying - but as far as I can tell the current problems
| with the vaccine are mainly in the nitty-gritty details of
| actually making it in the first place. Right now the
| companies doing that can basically write their price.
| tzs wrote:
| In the case of mRNA vaccines, according to what I've read the
| limiting factor is that they depend on specialized precursors
| that very few companies can make.
|
| Before the COVID-19 mRNA vaccine all mRNA vaccines that had
| been developed for humans didn't make it past testing. There
| was no need to have the ability to make them beyond what was
| needed for research and testing.
|
| And if one of the prior human mRNA vaccines had looked good
| in the middle of the phase III trial, the low manufacturing
| capacity would not have mattered. A normal phase III trial
| takes years, and the diseases the vaccines were for were not
| pandemics. So even if it takes a couple years to get up to
| the needed capacity, that would be fast enough.
|
| With COVID-19 mRNA vaccines, we've got (1) an emergency use
| authorization rather than a normal approval, so a much
| shorter time between finding out that the thing works and the
| start of consumer distribution, and (2) it's a pandemic so
| the number of doses needed is very very high. That's the
| worst possible combination.
| xiphias2 wrote:
| I read that the precursor was using an animal and there is
| a way to make it artificially (which was not approved by
| the FDA so far).
|
| I just wish governments were focusing on helping in ramping
| up manufacturing instead of using the current crisis for
| stealing as much money as possible (which is happening in
| my country).
| atonse wrote:
| Yeah but for that reason I'm very thankful that the
| government DOES have a monopoly on this process. That'll
| ensure the vaccine goes to the people that need it the most
| first, not just the people that can be gouged the most.
| techsupporter wrote:
| _Edited to add:_ I 'm not sure what's controversial about
| this? What did I mess up here? People seem to disagree but
| aren't, as of about an hour after I replied, saying why.
|
| In a way, we're seeing this happen at the national/country
| scale already. Countries that can afford it ("that can be
| gouged the most") are buying hundreds of millions of doses
| and the systems that are supposed to be getting doses to
| countries that _can 't_ afford it appear to be going
| wanting.
|
| That's the problem with health care as a capitalistic
| market. There's no upper bound on what someone would want
| to pay to preserve either their life or the life of someone
| they care about. The only limit is on the resources that
| person has access to, and people will make some screamingly
| bad long-term decisions in order to satisfy that short-term
| need for cash.
|
| If we did as the grandparent proposed and opened something
| like a bidding market for vaccines, you'd absolutely have
| GoFundMe and whatever the digital equivalent of yard sales
| are for people who are desperate to get the vaccine but
| don't have the money. Hell, I already see "please venmo me
| some cash so I can shelter-in-place away from my relative
| who has COVID because I can't afford to catch it myself as
| I'm the only person who makes money for my household."
| WallWextra wrote:
| There aren't many people with the expertise to produce the
| vaccine, and they're all already working on the existing
| production lines. The lead times are just inherently long
| here; takes months to start up a production line.
| gens wrote:
| Your words anger me.
| ch4s3 wrote:
| I would normally argue this case, but "factories" is sort of
| hand-wavy here. The factories dumping out the feedstock are
| all producing enough to meet a higher level of production.
| The mixing step is the bottle neck, and is a really hard,
| expensive process to scale up. Demand for the vaccine is
| likely to dry up in a year or two, and companies don't want
| to drastically over shoot building out expensive single
| purpose tooling.
| Mediterraneo10 wrote:
| > Demand for the vaccine is likely to dry up in a year or
| two
|
| Aren't many scientific advisors saying that 1) it will take
| years to vaccinate the developing world, and 2) risk groups
| may need annual booster shots in perpetuity to deal with
| mutations?
| cptskippy wrote:
| Potentially but that's not definite. No company will risk
| profits to invest in an unknown short term demand.
| They're fine letting people languish so they can ensure
| maximum profit.
| tomp wrote:
| You're simplifying this thing beyond reasonable.
|
| Several counterpoints:
|
| (1) "profit" is just another way of saying "effort".
| Would you try and work hard and risk your own money if
| you knew you weren't getting paid for it? If you _say_
| "yes", _do_ you actually do that?
|
| (2) they're probably used to it in this industry, but
| these pharma companies are really getting more hate than
| praise these days. "Damned if you do, damned if you
| don't." Except that they're not actually damned if they
| don't, they wouldn't be in the news at all!
|
| (3) same argument as above, except r/pharma/West. People
| here developed an amazing technological post-industrial
| civilisation over centuries, and now we can use this
| technology to rapidly produce vaccines... yet we're
| getting all the hate for not producing, manufacturing,
| distributing it _fast enough_.
|
| A bit unfair, don't you think?
| ch4s3 wrote:
| Well yes, but you still don't want to overbuild capacity.
| tmzt wrote:
| This may be true, but isn't vaccine fundamentally a
| delivery mechanism for a custom mRNA strand?
|
| If you build up the infrastructure you could quickly
| deliver a vaccine for another disease or practically any
| genetic therapy that could be delivered the same way.
| Moderna also has an advantage in that the logistics
| required are simpler.
| GhostOT wrote:
| Is there any evidence that paying 5x the price would actually
| result in a faster rollout of the vaccine? At a certain scale
| and timeline you can't throw money at the problem anymore
| there's a finite limit to how fast our global infrastructure
| can operate.
| pc86 wrote:
| The only thing it would result in is a faster rollout of
| the vaccine to _low-risk individuals with money to spend_.
| Distribution is currently [ /supposedly] roughly correlated
| to risk and public exposure in the early phases. High-risk
| people with money would just have to spend money they
| otherwise wouldn't. So this type of plan would come at the
| expense of high-risk people without money.
|
| This proposal is literally about putting high-risk people
| at _greater risk_ - and by extension, killing them - so
| low-risk people with money can feel a little better about
| eating at a restaurant and drinking at a bar on a Friday
| night.
| tomp wrote:
| Do you feel the same way about Tesla? _"These selfish
| rich people just wanna feel better about themselves
| driving their EV vehicles that noone else can afford!"_
| Yet the end result is, that more people can now afford
| EVs than otherwise could.
|
| I know it's a bit different with Covid vaccines (AFAIK
| they were largely sponsored by governments), but the
| underlying principle of your argument is just wrong -
| it's _good_ that rich investors sponsor new technology
| (even for selfish reasons!) because that makes technology
| available to everyone, sooner!
| jowsie wrote:
| I think comparing driving a Tesla when plenty of other
| cheaper forms of transport exist, with a vaccine to a
| currently ongoing pandemic that is literally killing
| people and to which there is no other available vaccine
| option, is a tad on the ridiculous side.
| cptskippy wrote:
| Free market ignores need and just exploits want.
|
| Regulation ensures those in need receive it.
|
| Scarcity ensures demand, supply erodes price.
|
| The ability for companies to charge what they want for the
| vaccine would ensure only those that could afford it would
| receive it, and there wouldn't be additional capital
| investment because that would dilute profits.
| throwaway9980 wrote:
| Needs are wants with greater urgency. Demand is ensured by
| the ongoing widespread death associated with the virus.
| Government should stand ready to pay a large price to
| ensure supply and provide subsidy for those with less
| means. Regulation, in this case, introduces inefficiency.
| Inefficiency, in this case, costs lives.
| xiphias2 wrote:
| Regulations price lives of old people at about $500 right
| now (vaccine price / death rate).
|
| The only government that didn't try to get the cheapest
| price for the vaccine is Israel, and we see the impressive
| results already.
| gambiting wrote:
| 5 times 0 is still zero. Also I hate everything your comment
| represents. From top to bottom. Nothing against yourself
| personally of course.
| newacct583 wrote:
| There's absolutely no evidence that this is the case. Money
| can't buy things instantly, the vaccine ramp is progressing
| very well as it is, and if you want to claim that a giant
| check would somehow produce more shots in arms you need to
| make that case with data. There are only so many units of the
| nanolipid production equipment available, and only so many
| factories that can make more, and only so many engineers who
| know how to operate those factories.
| Caligatio wrote:
| Please do not bring the American healthcare mentality to a
| product that is needed by literally everyone. The minute
| people can spend 5x to get the vaccine means that people will
| need to spend 5x to get the vaccine.
| Slartie wrote:
| Do you have any source or proof regarding that "retroactively"
| claim?
|
| Because AFAIK they only started to bill customers for 6 doses
| per vial when they received official regulatory approval for
| the 6th dose. Vials delivered earlier were not affected, so any
| 6th dose gathered from them was effectively free.
| faitswulff wrote:
| You are correct, it was not applied retroactively:
|
| > Gottlieb, the former head of the FDA, clarified that the
| change is not going to be applied retroactively, meaning that
| all vials previously shipped out are counted as containing
| five doses.
|
| https://www.cnbc.com/2021/01/25/pfizer-board-member-
| gottlieb...
| newacct583 wrote:
| You seem to imply that that's somehow a trick or a bad thing,
| but the _only_ valid purpose to counting number of vaccines
| shipped[1] is as a proxy for the number of vaccines delivered.
| The extra doses in a vial were a happy accident, not a trick.
| And the number we actually want to know is the one we 're being
| given now.
| IgorPartola wrote:
| If a vaccine vial was shipped in December and was given
| wholly to one person, that's one dose. You can't claim it was
| two back then because it couldn't have been used as two.
|
| The real problem I see is that we count vaccine doses as one
| shot. For Pfizer and Moderna two shots = one dose. It is
| misleading to show a two vial dose as two doses.
| weaksauce wrote:
| the vials hold 5 shots and then they were approved to hold
| 6 shots. this was good because the packaging of the vaccine
| was one factor in slowing down the spread of the vaccines.
| IgorPartola wrote:
| But you can't count that retroactively for vials where 5
| shots were administered and at that point the vial was
| empty. You can only count that for unopened vials.
| s1artibartfast wrote:
| Correct, but nobody tried to do that.
| DanBC wrote:
| You can count 6 shots if 6 shots were given. That's
| what's happening.
| skybrian wrote:
| Right, but this is a dispute over something they didn't
| do.
| mbreese wrote:
| I didn't think that was the case. I thought that the
| vials held the same volume regardless. But each vial has
| some "extra" to account for lost volume in extraction.
| Let's say it had 5% extra per dose. That's almost enough
| for a complete 6th dose, but not quite. But, if you use a
| more efficient syringe, then you might save an additional
| 1% per dose. So now, your 5 dose vial has enough "extra"
| volume for a complete 6th dose. And the manufacturing
| doesn't need to change.
|
| That's the benefit.
|
| Note: this was always accounted for as "extra" doses. It
| was part of the plan that there would be extra volume for
| each vial that could be pooled together for extra full
| doses. But because they are "extra", you couldn't plan on
| there always being that extra dose (or over the course of
| a day how many extra doses).
| mercurywells wrote:
| You do need a specific type of syringe in order to
| extract the 6th dose correctly and it was not the case
| that 100% of the distribution was set up with that
| particular syringe in mind.
| raverbashing wrote:
| Not retroactively since it would need the ok from the regulator
| (and then start dispensing the half doses)
|
| I think Pfizer could only start counting the 6th doses after
| the agencies Ok'd it (and the special syringes were procured)
| tarkin2 wrote:
| Is the title confusing?
|
| On first read, I thought it was something that neutralizes
| antibodies, rather than antibodies that neutralize the virus.
|
| My layman's assumption was that the antibodies would always
| neturalize, so adding the adjectives threw me off the meaning.
| paxswill wrote:
| (Summarizing things I've picked up from reading Derek Lowe's
| blog [0])
|
| Not all antibodies are neutralizing. Antibodies can only bind
| to a certain part of pathogens, but if an antibody binds to
| something it might not disrupt what that thing needs to do to
| infect the body. Relating this to SARS-CoV-2, it looks like if
| an antibody bind to something other than the spike protein, the
| virus can still infect cells. As another example, most people
| have been exposed to at least some other coronaviruses, and of
| that group, some of those people have developed antibodies that
| react to SARS-CoV-2. A recent paper [1] looked at if these
| "cross-reactive" antibodies were helpful in preventing COVID,
| but it looks like they're non-neutralizing as they couldn't see
| any effect.
|
| 0: https://blogs.sciencemag.org/pipeline/
|
| 1:
| https://blogs.sciencemag.org/pipeline/archives/2021/02/10/do...
| SAI_Peregrinus wrote:
| Not all antibodies neutralize the (or any) virus. Some just
| mark virions for immune cells to acttack, but won't stop the
| infection process.
| boulos wrote:
| The results in Figure 3 are certainly promising. Has anyone been
| able to find the mentioned supplementary material though?
|
| > A post-hoc exploratory analysis of immunogenicity in subgroups
| of participants aged >=55-<65, >=65-74 and >=75 years was
| performed (Tables S6 and S7). Increases in levels of anti-SARS-
| CoV-2-spike bAb and nAb at days 29 and post-second vaccination at
| both the 50 and 100 ug doses were generally comparable across the
| age subgroups and with those observed in the younger (18-55
| years) study participants. Seroconversion rates were also
| comparable across the age groups and with those in the younger
| participants. It should be noted that the small size of the >=75
| year-old subgroup (n=22) precludes definitive conclusions to be
| made.
|
| There doesn't seem to be any link to supplementary material at
| either the Elsevier page [1] nor the NIH page [2]. The clinical
| trial registration [3] suggests that there was an update just a
| few days ago, so perhaps they're just waiting to upload a new
| PDF?
|
| [1]
| https://www.sciencedirect.com/science/article/pii/S0264410X2...
|
| [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/
|
| [3] https://clinicaltrials.gov/ct2/show/study/NCT04405076
| polote wrote:
| Let's hope that half half doses works too
| johnchristopher wrote:
| Homeopathy? Homeopathy!
| unicornporn wrote:
| Stirred, not shaken!
| JohnTHaller wrote:
| Take a bit of blue Ford Mondeo...
| StavrosK wrote:
| My God man, do you want people to overdose?!
| overcast wrote:
| The Moderna dose is already more than 3x the dosage of the Pfizer
| ones. 100mcg vs 30mcg. Would be great if they could cut that down
| and still be effective.
| HenryBemis wrote:
| So... if that plays out, perhaps split the doses in half, cover
| twice the people, so we can all go back to our normal pre-COVID
| life (or what's left of it).
|
| Of course this won't double the number of people vaccinated
| since Moderna doesn't cover 100%. But every little helps.
| downrightmike wrote:
| We're not going back to pre covid lives period. Even if
| everyone was vaxxed there would still be more moderate cases
| that our hospitals can handle. And then that allows the virus
| millions of chances to mutate and then, just like we're
| seeing with the UK and South Africa strains. Which as we're
| seeing all but nullifies the vaccine. The vaccines we're
| seeing are only 10% effective against the SA strain.
| Statistically >5% is great, but that's not a risk the vast
| majority of people want to run with.
| Zanni wrote:
| The efficacy number is about preventing cases of Covid-19,
| but in fact, even the "low" efficacy vaccines are extremely
| good at preventing severe illness and death. Once we get
| everyone vaccinated, we should be good.
|
| https://www.vox.com/22273502/covid-vaccines-pfizer-
| moderna-j...
| grey-area wrote:
| _The vaccines we 're seeing are only 10% effective against
| the SA strain._
|
| This is not accurate.
|
| The AZ vaccine was only 10% effective in a study in SA.
| That's the only one that was shown to be vastly less
| effective.
|
| The Pfizer vaccine is believed to be effective against the
| SA variant (though I think it used In Vitro studies) and
| there are lots of other vaccines on the way. We will get
| this under control but it will be a long slow process over
| several years.
| downrightmike wrote:
| So far it is the only one.
| ingenium wrote:
| I believe Moderna was also shown to be effective.
| sschueller wrote:
| If we vaccinate enough people to get the fatally rate well
| below the flu there is absolutely no reason not to go back
| to the old way. There is no 100% safe but there is a level
| at which hospitals are not overwhelmed and people are
| accepting the risk of being alive.
| Denvercoder9 wrote:
| > We're not going back to pre covid lives period.
|
| We are. Most people, myself included, won't accept living
| like this forever. If vaccination fails and no treatment
| will be found, we'll expand healthcare capacity and accept
| that people will die.
| [deleted]
| downrightmike wrote:
| We're already taxing our medical system. Personnel will
| wear down.
| Denvercoder9 wrote:
| Hence I said to expand healthcare capacity. If there's
| not enough personnel, we should educate and hire more
| personnel. I'm not saying this is something we should do
| tomorrow -- only in the hypothetical case that we haven't
| found an effective prevention and/or cure in 5 years or
| so.
| imwillofficial wrote:
| Didn't we move this way with the flu?
| downrightmike wrote:
| People couldn't behave back then for real reasons, most
| people that are the problem today are just spoiled brats.
| Back then they didn't have the century of epidemiology
| knowledge that was outright ignored and trivialized.
| IgorPartola wrote:
| Yeah. And a dose of vitamin C at 3000 mg is 30,000 larger than
| Moderna's. You are comparing apples and cheese. Simply weighing
| them won't tell you anything.
| imwillofficial wrote:
| The vitamin C will do more for you. Throw in vitamin D and
| studies show it's far less of a risk profile than any of the
| vaccines (I haven't looked at Russia's yet)
| CyanLite2 wrote:
| They're not the same formulation, so you can't compare the
| dosing, it's Apples vs. Walnuts
|
| The problem with the 50mcg dose is that there is justifiable
| concern that if you error on the side of low-dosing that the
| mass vaccination won't work and the public sentiment will turn
| against it. We'd rather see 95% efficacy with the 100mcg than
| risk the POSSIBILITY of 60% efficacy with the 50mcg dose. We
| literally have one shot (or two, pun intended) to get it right
| the first time. Only 4 months ago, most of the world hadn't
| even heard of mRNA vaccines or somehow believed it was micro-
| chipped by Bill Gates. Much of that nonsense has gone away
| because they're getting unbelievable efficacy that's higher
| than the traditionally-made vaccines from Astra-Zeneca and JnJ.
| protomyth wrote:
| I gotta say that the dose really is a pain in the arm. We ended
| up on the list at work and the first dose hurt for a good four
| days. Others had a similar outcome. My father got the first
| Pfizer and he reported no issues with his arm hurting. I doubt
| he was not telling the truth on that one.
| blhack wrote:
| Got Pfizer. Zero arm pain. Same for my wife.
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