[HN Gopher] Pfizer vaccine appears effective against mutation in...
___________________________________________________________________
Pfizer vaccine appears effective against mutation in new
coronavirus variants
Author : awnird
Score : 614 points
Date : 2021-01-09 03:48 UTC (19 hours ago)
(HTM) web link (www.cbc.ca)
(TXT) w3m dump (www.cbc.ca)
| noncoml wrote:
| Slightly off-topic, but I don't have any other good forum to ask
| that.
|
| Once we are done with COVID, will the new vaccine methods enable
| us to develop vaccines for virus that we couldn't do before. E.g.
| maybe HIV?
| kdps wrote:
| That's what BioNTech has been researching for years. BNT162b2
| is, slightly exaggerated, a by-product.
|
| From https://en.wikipedia.org/wiki/BioNTech:
|
| _It develops pharmaceutical candidates based on messenger
| ribonucleic acid (mRNA) for use as individualized cancer
| immunotherapies, as vaccines against infectious diseases and as
| protein replacement therapies for rare diseases, and also
| engineered cell therapy, novel antibodies and small molecule
| immunomodulators as treatment options for cancer._
| jojobas wrote:
| HIV is hard as it attacks the very immune cells that come to
| get it.
| raducu wrote:
| It's not just that. People do develop neutralizing antibodies
| against HIV.
|
| HIV, like other retroviruses, embedds itself in the cell DNA.
|
| Some cells remain dormant for weeks and then start producing
| virions.
|
| So the other problem with HIV, even if it didn't attack
| immune cells, is the hidden virus reservoir, I guess, just
| like other incurable viruses, like herpes and some hepatitis.
| fastball wrote:
| Right but if you're vaccinated, you'd hope the immune
| system could attack HIV before it could take hold.
| raducu wrote:
| I really don't know enough about immunology to answer
| that -- but I presume most neutralizing antibodies wane
| over time.
|
| If you take antiretrovirals you're very unlikely to
| become infected with HIV, even if you take it after
| initial exposure (but do your own research on that), but
| as soon as you stop, you lose that protection -- same
| with antibodies (not sure how a vaccine would help T-cell
| immunity if HIV infects T-cells).
| inglor_cz wrote:
| CRISPR can edit herpes simplex virus out of cells, so maybe
| it can do the same for HIV.
|
| https://www.globenewswire.com/news-
| release/2019/11/18/194889...
| raducu wrote:
| Wow, thanks, that's really interesting!
| tachyonbeam wrote:
| Maybe? The nice thing about mRNA vaccines is that the formula
| can be adjusted very rapidly (weeks). I feel like if there was
| a way to tweak the formula fast enough, we could react as fast
| as the different viral strains mutate. We would need to change
| the regulatory framework though. Having to do 3 phases of
| clinical trial involving tens of thousands of participants
| makes it hard to adapt fast enough.
| mrtesthah wrote:
| > we could react as fast as the different viral strains
| mutate
|
| The number of mutations is proportional to the number of
| people currently infected. The faster the virus spreads the
| more variants will be created. The fact that the N501 variant
| spreads faster seems to imply that the rate of mutations is
| already in the process of accelerating.
|
| It may make more sense to use evolutionary modeling and
| analysis of existing SARS-type viruses to create antigens
| robust to all expected mutations. Here's one such bit of
| research:
| https://www.biorxiv.org/content/10.1101/2020.11.17.387092v2
| rtx wrote:
| So we will see weekly news about new strains and new vaccines
| to prevent them from spreading. This might be a long drawn
| process.
| gurleen_s wrote:
| Is the risk that's being assessed by these trials coming from
| the delivery method of the vaccine? Perhaps maybe there's a
| way to get around some of those regulations.
| BillyTheKing wrote:
| doesn't the regulatory framework allow such changes though?
| afaik we aren't doing any phase 3 trials for the annual flu
| shot, or are we? (genuine question) But if we aren't,
| couldn't we just expand this to also take into account the
| Covid-shot?
| bluGill wrote:
| The flu shot gets a special exception to the process. They
| study safety every year, but not effectiveness. This takes
| months off the development time.
| lvs wrote:
| While this is indeed a new vaccine modality, it doesn't change
| the dynamics of vaccinology appreciably. Things that were
| challenging vaccine targets in the past will likely remain
| challenging.
| hobofan wrote:
| Doesn't it change the dynamics insofar as that you have a
| straightforward path from virus -> its mRNA blueprint,
| without more specialized and likely costly engineering of
| e.g. a adenovirus? This should then allow for broader
| protection against viruses with many strains e.g. a HPV
| vaccine cocktail that protects against all ~100 known strains
| vs. just the 9 it currently does.
| raducu wrote:
| Some influenza antibodies destroy certain neurons in your
| brain and you develop narcolepsy.
|
| This is both true for natural infection and first
| generation vacines.
|
| Later generation vaccines avoid this by not presenting
| certain proteins.
|
| My point is, you can't just include hundreds of protein
| variants without a lot of trials.
| beagle3 wrote:
| Do you have a reference for this? It was my assumption
| too, reading about the Pandemrix vaccine, but I didn't
| find any dependable references for this.
| bluGill wrote:
| Even if he is wrong about how it works, because of the
| potential for unknowns they need to study it in a trial.
| There is a lot we don't know about biology.
| hobofan wrote:
| I'm not suggesting to include new strains on the fly
| while they are discovered without trials. The same way
| they had to do trials for Gardasil-9 after already having
| Gardasil, they could do the same just with a wider
| cocktail.
|
| In the optimal case you would attempt the 100+ cocktail
| and don't have any unreasonable side effects from them.
| Of course if there is a single variant in there that
| causes side effects you would need a ton of trials to
| triangulate which one causes them, but there is no
| guarantee that that is necessary or that you wouldn't run
| into that variant when you just adding 5 new variants in
| an iteration.
| AhmedHassan2027 wrote:
| Thanks to pfizer to take affective medicine to open the world
| allendoerfer wrote:
| Also thanks to BioNtech for developing said medicine.
| phreeza wrote:
| What I haven't seen widely discussed regarding the new variant is
| whether the higher infectiousness means herd immunity will be
| achieved later. From my amateur understanding of the SIR model,
| this should be the case.
|
| So ultimately we may not achieve herd immunity except with
| mandatory vaccination campaigns.
| 7OVO7 wrote:
| good for all those suppressed people
| alevskaya wrote:
| Sadly, note that the study talked about here [1] is investigating
| the effect of the N501Y mutation, not the more worrying E484K
| mutation found in the South African 501.v2 strain that likely
| does escape antibody drugs and reduces neutralization by
| convalescent sera from past infections. [2]
|
| [1]: https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1
|
| [2]: https://www.biorxiv.org/content/10.1101/2020.12.31.425021v1
| jb1991 wrote:
| I wonder why it says:
|
| > works against a key mutation in the highly transmissible new
| variants of the coronavirus discovered in Britain and South
| Africa
| dmix wrote:
| Both the South African and UK variant seem to be under the
| name 501Y.V2 but the South African version has a mutation not
| seen in the UK strain:
|
| > The variant in South Africa carries two other mutations in
| the spike protein (E484K and K417N, among others) which are
| not present in the U.K. strain
|
| This three day old article also anticipated this study
| results:
|
| > While scientists believe the U.K. variant is not likely to
| affect the efficacy of the vaccines currently being rolled
| out in the West, there is more uncertainty regarding the
| other strain.
|
| https://www.cnbc.com/2021/01/06/south-africa-covid-
| strain-a-...
|
| I'm guessing they are both of the same "strain" but of
| different "variant". But I don't know enough about how virus
| taxonomy works to validate that. Sounds like two levels of
| mutation...
| zebrafish wrote:
| Discussion of [2] on /r/covid19:
| https://www.reddit.com/r/COVID19/comments/kqz7y5/comprehensi...
| TheRealSteel wrote:
| Does this mean there's now a variant that is immune to all the
| vaccines, and we're basically back at square one with the
| pandemic?!?! :( or am I misunderstanding? Is it still protected
| against from mRNA vaccines, but just not prevented by immunity
| from past infections?
|
| I have no knowledge of biology whatsoever.
| mckirk wrote:
| From what I've gathered, it's more like: It's likely that the
| vaccine will have reduced efficacy (seen over the whole
| population) against this new strain. That's because your
| immune system essentially learns to recognize a random part
| of the virus, and if it ends up "training" itself using that
| part of the spike protein that's changed in this strain, it
| won't detect the virus.
| graeme wrote:
| Not square one. It's unlikely there would be 0% efficacy. But
| it could be less.
|
| But also not square one because it takes literally a day to
| redesign mrna vaccines for new variants. Then hopefully they
| can be approved faster the second go and
| manufactured/distributed more quickly.
|
| But I'd say all northern hemisphere countries should do their
| best to focus on local elimination in summer 2021. Most of
| europe had it in reach summer 2020 but decided to reopen
| early and keep the virus at a low level.
|
| That was an abject failure. It probably only would have taken
| another month of heavy restrictions to eliminate.
|
| The mutations we're seeing in the winter of high case volumes
| caution against doing another cycle like this.
| TheRealSteel wrote:
| Great, thanks for the info. mRNA tech really is amazing!!
|
| I agree. Everywhere should've pursued elimination strategy
| like Australia and New Zealand, and even at this late stage
| would be the best option.
| Mediterraneo10 wrote:
| > Everywhere should've pursued elimination strategy like
| Australia and New Zealand
|
| Australia and New Zealand were very unusual in having
| that possibility, not everyone could have followed such a
| strategy. The EU had to move thousands and thousands of
| migrant agricultural workers from Eastern Europe to
| Western Europe for the harvests, otherwise there would
| have been scarcities of common foodstuffs. Also goods
| move through Europe largely through freight trucks that
| mean drivers moving about, not container shipping like
| the two island nations you mention.
| graeme wrote:
| I'm in Atlantic Canada, where we had eliminated it
| locally. We moved in agricultural workers, it was fine.
| We just had an isolation requirement and testing.
|
| We have freight trucks from the US too! A lot of
| obstacles are not, in fact, insurmountable. The actual
| issue is that most places weren't aiming at elimination.
| Mediterraneo10 wrote:
| > We moved in agricultural workers, it was fine. We just
| had an isolation requirement and testing.
|
| As you might remember, there was a shortage of tests the
| first time that the EU needed to move its agricultural
| workers en masse (which happened already in the spring -
| harvests in Spain are more or less continuous, unlike
| Atlantic Canada where it is much more restricted
| seasonally). Also, many of those agricultural laborers
| live in precarious working conditions that the state has
| little insight into, and arranging any kind of isolation
| on short notice was not possible.
|
| The EU was not aiming at total elimination because the
| virus had already spread throughout the bloc practically
| before the authorities were even aware of it and again,
| these are not island nations.
| graeme wrote:
| Sure but you had until the end of August to end it.
| Spring was the early days. And it would have been
| conceivable to try to eliminate it locally in sectors
| _other_ than agriculture. Deal with the easy buts first
| and then the hard bits after. Often the hard bits become
| easier in so doing.
|
| You could have kept internal border controls except for
| essential work. We did that in Atlantic Canada.
| Australian states did that. We're just as integrated as
| the EU is! We never had a border at any point in our
| history. So we set one up.
|
| There are non islands that more or less eliminated it.
| China, vietnam for example.
|
| Harder in the EU? More complicated? Absolutely. But the
| policy the EU pursued was an abject failure, so merely
| saying "there would have been difficulties" doesn't show
| that elimination would have been worse. The places that
| reduced covid better generally saw better economic
| results too.
| Mediterraneo10 wrote:
| > You could have kept internal border controls except for
| essential work.
|
| Lack of internal borders in the EU is one of the most
| important features of the bloc, both in terms of
| maintaining close integration that could prevent more
| intra-European wars and in terms of mere everyday
| convenience. I would gladly sacrifice the demographic
| most at risk of COVID (about half of all deaths in the EU
| so far have been in care homes) in order to avoid
| internal borders.
|
| Also, China has been able to eliminate COVID (and even
| that is subject to doubt) only through civil-rights
| violations that the West would not tolerate. Pointing to
| China and saying "They did it, so the EU could too"
| misses the point. Vietnam was able to avoid a surge in
| COVID cases only because they hadn't yet got the huge
| number of cases that the EU had first without even being
| aware of it; of course if somewhere else is already
| suffering, and you aren't, you can close the borders and
| avoid the problems from the start.
| FuckButtons wrote:
| That was very much the opinion of the immunologists I have
| been reading the opinions of recently. Giving this virus
| opportunity to mutate through allowing circulation is
| playing with fire next to a dynamite factory.
| Mediterraneo10 wrote:
| > But I'd say all northern hemisphere countries should do
| their best to focus on local elimination in summer 2021.
|
| This isn't realistic. Fatigue with COVID restrictions has
| already set in across Europe: people are wearing masks in
| sloppy ways (not covering the nose, or even just putting
| the mask over their chin) and returning to socializing or
| even leisure travel. The authorities know this, and while
| they can do things like keep restaurants and theatres
| closed, they appear to feel little democratic mandate for
| using the police to enforce strict social separation
| between individuals. And that is in the winter: once the
| warm weather comes back, expect even more flaunting of
| restrictions.
| graeme wrote:
| That happened summer 2020 and look where things ended up.
| There are a few factors I think you're missing:
|
| 1. The virus is seasonal. Substantially less restrictions
| are needed over the summer. Outdoor socialization really
| isn't high risk
|
| 2. School is out. This naturally lowers spread
|
| 3. A bunch of people will be vaccinated. This will surely
| make it easier
|
| 4. We'll probably have new rapid tests by the summer.
| They go a long way to reducing spread without much
| inconvenience. Michael Mina has been banging his head
| against the wall for months to get people to listen:
| these can be as effective as lockdowns and much less
| burdensome.
|
| 5. At least some countries will figure this out, go for
| elimination, and require a vaccine/negative test for
| entry and make travel arrangements with other covid zero
| areas
|
| Now it might be the vaccines work perfectly, no mutant
| strains escape them, and we won't have a repeat of this
| in fall/winter 2021/22.
|
| But if that scenario does seem likely them elimination is
| overwhelmingly the best option. And society that can't
| pull itself together to do that will live in a purgatory.
| pageandrew wrote:
| Does the 501.v2 strain resist vaccine antibodies as well, or
| only things like the antibody cocktail / convalescent plasma
| therapy?
| whoisburbansky wrote:
| The first paper describes the effect of mRNA based vaccine
| derived serum on both variants, showing that both variants
| are affected about equally by the vaccine, if I'm not
| horribly mistaken?
| alevskaya wrote:
| The first study is only studying the effect of the N501Y
| mutation as found in several emergent strains, not the
| E484K mutation.
| whoisburbansky wrote:
| Yes, sorry, I phrased that badly. I meant N501 and Y501
| when I said both variants here.
| alevskaya wrote:
| What I meant by sera above was general adaptive immunity.
| It's likely to partially resist past immunity from both
| vaccines (esp. from the spike-only vaccines: moderna, pfizer,
| etc) and natural infections from older strains. We'll
| probably know a lot more about it soon, but we may need to
| update our vaccines to include this mutant class.
| f430 wrote:
| > does escape antibody drugs and reduces neutralization by
| convalescent sera from past infections
|
| what does this mean in plain words? this SA variant has a
| totally new evasion system?
|
| what exactly are we dealing with here? what causes it to
| rapidly mutate like this?
| jonplackett wrote:
| It's just evolution - we put social distancing and masks in
| place, so variants that can overcome those emerged and
| spread.
|
| Think of it like antibiotic resistance - our crappy attempt
| at lockdown was like not finishing the course. We gave it
| loads of places to multiply but didn't finish it off so it
| just adapted
| FuckButtons wrote:
| The mutations don't arise because of selection pressure
| against masks and social distancing, that is dangerously
| wrong. They arise in an individual patient who has a poor
| immune response who can't clear the virus for a long time.
| As their immune response tries to clear the virus it adapts
| to be more effective over many generations inside that
| patient. That's why we have distinct lineages, each of
| these variants with multiple distinct mutations probably
| arose in a single person.
| esyir wrote:
| It's a virus. Mutation to avoid detection is par the course.
|
| Essentially, each replication means mutation, and over time,
| variants emerge. Think of why you need a seasonal flu vaccine
| and not one flu vaccine.
| dnautics wrote:
| Viruses are typically rapidly mutating so you should consider
| them to be a fuzzy statistical ensemble around the "official"
| sequence, even in one patient. Therefore these viruses can
| facilely jump over hills in the gradient descent of
| optimization; but keep in mind optimization is not just a
| one-factor thing. If you are interested in this the keyword
| is "viral metagenome"
|
| An E to K mutation converts a surface negative charge to a
| surface positive charge. So if your antibodies were expecting
| a negative charge and therefore putting positive charges near
| that place when they attach to the virus, the polarity on the
| mutant has now shifted and the antibodies will be repelled
| from the mutant virus.
| Erlich_Bachman wrote:
| > Therefore these viruses can facilely jump over hills in
| the gradient descent of optimization
|
| It warms to see that the similarities of some aspects of
| biological life to the current AI/ML terms has entered the
| lexicon, well at least on HN crowd. The fact that it makes
| a lot of sense to use those terms hints that we might
| indeed be on the right track to building AGI and
| understnding the life itself in general.
| hutzlibu wrote:
| "The fact that it makes a lot of sense to use those terms
| hints that we might indeed be on the right track to
| building AGI "
|
| But there is also the danger of false analogies doing
| damage, by creating the illusion of understanding
| something because the wording feels familiar.
|
| There are no doubts similarities, but that does not mean,
| it is the same.
|
| That happened a couple of times already with progess in
| technology and then simplified applied technical models
| to biological life.
|
| So sure, I think so too, that we are on the right track,
| I am just a bit more hesistant.
| mvanaltvorst wrote:
| Gradient descent is a subset of survival of the fittest,
| described by Darwin in 1800-1900, and has been in applied
| in computer science since the 70's. An AGI will probably
| use some form of gradient descent during its training,
| yes, but I wouldn't argue that this has brought us even
| close to an AGI.
| dnautics wrote:
| This is wrong. Gradient descent derives from multivariate
| calculus, not evolution.
| dnautics wrote:
| Objective cost surfaces have been around way longer than
| ml. It's been in the genetic algorithm lexicon for a long
| time, and more true to form, in stuff like actual
| potential energy diagrams of high dimensional degrees of
| freedom spaces in enzymology. Also having been a
| professional biochemist and worked in AI infrastructure,
| I know the commonalities well and know how to avoid faux-
| amis.
|
| Note that this process is NOT backpropagation.
|
| "The fact that it makes a lot of sense to use those terms
| hints that we might indeed be on the right track to
| building AGI and understnding the life itself in general"
|
| Nope, it's a residual of the fact that AI stole ideas
| from other fields, and ran with the terminology as
| marketing. Sometimes even to the point of extreme
| divergence from the original ("neural" nets).
| quonn wrote:
| How is there gradient descent or even a gradient in
| biological mutations? If anything there could be an
| analogy to undirected trial & error as in genetic
| algorithms.
| RobertoG wrote:
| I think that they are using "gradient descend" when they
| should be using "space of the problem". Otherwise is a
| good comment.
| Erlich_Bachman wrote:
| It's directed by the survival and spreading of the virus.
| jsinai wrote:
| meta, what if it was just GPT-3 commenting and there was
| just leakage from the ML community
| martin_bech wrote:
| Afaik not all rapidly mutating, HIV seems to be mutating at
| a rapid pace, yet measels apparently largely never mutates.
| dnautics wrote:
| That's why I said typically, not always.
| sudosysgen wrote:
| The majority of viruses do not mutate rapidly enough to
| evade immunity. The exceptions are virus with chronic
| infections because they can mutate much more easily, and
| some viruses like Influenza that can use antigenic
| shifts.
|
| It's really not typical. Even in all of the human cold
| coronaviruses, only one seems to be evolving its spike
| protein, and it does so quite slowly.
|
| If it was typical, we wouldn't see the amazing efficacy
| of vaccines against endemic diseases.
| whoisburbansky wrote:
| Am I reading the second paper correctly when I say this was
| conducted on a sample size of 11, and they found that the E484K
| mutation had saw no reduction in neutralization in some of
| those subjects? I'm trying to get a better sense of the numbers
| involved to figure out how much credence to lend to the dangers
| posed by the second mutation.
| alevskaya wrote:
| It's unlikely to _completely_ escape immunity - humans will
| raise antibodies against different regions of the spike
| protein, but it does seem to confer a pretty significant
| average resistance to patient sera. There's another study
| looking specifically at several different monoclonal
| antibodies against this mutation at:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723407/
| whoisburbansky wrote:
| When you say average here, is that in the sense of average
| resistance over time for a given patient or average
| resistance across a population? The paper seemed to imply a
| great deal of heterogeneity in individual responses to the
| variant, so significant average would just be something
| like part of the population affected very badly, another
| part not at all, vs everyone affected mildly?
| alevskaya wrote:
| Averaged over a population - some people will have
| resistant sera and others not depending on the parts of
| sars-cov-2 targeted by their polyvalent antibody
| response. Note that this is only looking at antibodies,
| not T-cell responses... so the clinical consequences are
| harder to predict, but it's certainly a bit concerning.
| whoisburbansky wrote:
| Ah, I see. Thanks, that clears things up quite a bit.
| It's potentially mildly bad news but not the end of the
| world, is what it sounds like then.
| robbiep wrote:
| No idea why the downvotes here (at initial time of
| writing), that's literally how the immune system functions,
| it's a random process and everybody's antibody DNA will be
| different to someone else's antibody sequence against the
| same antigen.
|
| No vaccine is training the body on the exact antibody to
| raise, it's training it to (hopefully, because sometimes
| the stochastic process missed) recognise particular
| epitopes.
|
| Important to also note that generally (and particularly
| during early infection) there will be many antibodies that
| recognise parts of an antigen.
|
| Affinity Maturation through somatic hypermutation is one of
| the most amazing processes the body does - look it up or
| for a very brief summary look at my notes on page 32 (or
| the whole mechanism of adaptive immunity from 27) with a
| little diagram on page 28
|
| https://www.dropbox.com/s/4ldgs4v9y99anm8/BCHM%203072%20Not
| e...
| l33tman wrote:
| It truly is. In early medschool we had a group student
| session on the adaptive immune system where we had to
| brainstorm on antibody generation and nobody in the group
| even came up with an idea remotely close to how it
| actually works. Robust and amazing. Talk about brute-
| force searching.
|
| Still, at this day my hope is that we'll be able to do
| the body's work even better at some point using computer
| designed antibodies (or similar) at least for therapies.
| There are some notable bottlenecks in the adaptive system
| where antigen fragments have to be broken down and shown
| to potential antibodies and this is a bit different
| between humans etc. The human antibody molecule is also
| very large and it's particular design doesn't fit some
| epitopes you'd want to hit (not an expert on it but I
| remember one of the HIV proteins having an area you'd
| want to train on but that can't accommodate the antibody
| variable fragments well).
| dnautics wrote:
| An N to Y mutation is associated with tighter specificity in
| binding protein protein interfaces. An E to K mutation is
| changing the surface charge from negative to positive so it
| shouldn't be surprising that it reduces antibody's ability to
| recognize, assuming it's in the most recognized pocket.
| Hopefully this will be a relatively easy cut and paste into the
| existing vaccine cassette if it turns out to spread really
| widely.
| JamesBarney wrote:
| I'm far more worried about the FDA and logistics than
| technical limitations.
|
| Even if you could make this fix in a day, it'll take months
| to get FDA approval, and then you still have to manufacture
| and distribute it. And by that time the populous will have
| gotten immunity the old fashion way.
| dnautics wrote:
| Indeed. And the likelihood of escape are worse the greater
| the infected population x time to new vaccine. I'm
| increasingly worried that covid-19 is the slow loris of
| viruses. Too slow and mild to warrant panic-mode measures
| (I don't mean lockdowns), just gonna be an annual
| millimation of the population.
| howlgarnish wrote:
| Aren't we in panic mode measures already? I'm not sure
| there's much more most countries can realistically
| implement even if there's a 10x more lethal variant.
| the8472 wrote:
| During initial containment china welded apartments shut
| and organized essentials deliveries by dedicated couriers
| for each city block. And then there's the option of
| military-enforced cordons. There are multiple levels of
| panic left untapped.
| howlgarnish wrote:
| That's why I said "most countries", because in (say) the
| US the government couldn't pull that off even if they
| tried. (For one thing, it's hard to weld shut suburban
| housing.)
| nicoburns wrote:
| Perhaps, but if the virus was as transmissible as sars-
| cov-2, but had a much higher fatality rate (say 60% like
| Ebola). Then you would get a lot more support for strict
| measures amongst the general population.
| dnautics wrote:
| I said "not lockdowns". I meant things like "strip down
| the phase testing" etc.
|
| I see no evidence we are doing that.
| meddlepal wrote:
| I think Parents point was that eventually we will have to
| give up on panic mode and accept deaths from this each
| year.
| partingshots wrote:
| For the vaccine to lose effectiveness, the mutation would have
| to drastically alter the spike protein of the virus.
|
| This is effectively impossible as the virus is dependent on a
| functioning spike protein in order to infect cells, and the
| machinery involved with the mechanics of the spike are
| extremely delicate. Errant mutations that would cause
| compositional changes to the shape of the protein are almost
| guaranteed to cause functional failure. Using terminology, this
| is what we call a highly conserved area.
|
| In both cases for the South African or UK strain, if you take a
| look at the areas where mutations have occurred, you'll see
| that the code responsible for generating the spike protein is
| basically completely unaffected. This will generally hold true
| for any successive future strains.
| [deleted]
| enchiridion wrote:
| While that may be true, I think that scale plays a role here.
|
| The ancestors of this virus were bouncing around between a
| relatively small set of humans and animals for a while before
| becoming SARS-CoV-2.
|
| Now with a significant portion of the world infected, it does
| not seem unreasonable that it would mutate. Although at that
| point it probably would not be considered the same virus
| anymore.
| hn_throwaway_99 wrote:
| This doesn't make much sense to me, given that coronaviruses,
| with spike proteins, have existed for eons, and humans have
| had lots of time to build up immunity to previous
| coronaviruses (ones that cause colds, for example). So there
| was something about the Covid-19 coronavirus spike proteins
| that was different enough where it didn't look like
| "familiar" coronaviruses, so I see no reason why it couldn't
| evolve further to evade whatever antibodies humans are able
| to build up to the vaccines.
| sudosysgen wrote:
| You can make multiple spike proteins that target the same
| receptor.
|
| This generally happens when a virus from another animal
| (and thus with a slightly different version of the
| receptor) adapts to humans.
|
| Basically, a gradient descent from a very different
| starting point ending up in a different local minima.
|
| The question is, is the spike protein at a local minima
| (very probably quite close to it), and could it jump to
| another local minima then? Most likely not.
|
| It's possible it will evolve to make our antibodies
| slightly less effective, likely as a trade off for
| infectiousness, but incredibly unlikely the spike protein
| would evolve to be unrecognizable to our immune systems.
| Historically, this doesn't happen all that often, except
| for viruses with chronic infections over years that can do
| a deeper search over the gradient, but even then it
| generally takes years to decades.
| dimgl wrote:
| This is extremely interesting. Thanks for this context.
| Detailed and thoughtful explanations like this help to
| understand the news.
| lawrenceyan wrote:
| Given the non-linear dynamics that proteins must live
| under, I like the usage of local minima as an analogy. It
| feels apt.
|
| Generally though, within the context of machine learning,
| one of the benefits of gradient descent, especially when
| stochastic, is that we can get past those local minima
| humps. Does this hold less true with respect to the
| process of sequence mutation that viruses go through?
| rolph wrote:
| you are speaking about a general case scenario, there is
| conservation of sequence region and variation of sequence
| region. to wit one protien encoding sequence has separate
| regions corresponding to regions of the product protien, the
| receptor binding domain[RBD] is a moderately conserved region
| ; the ImmunoAntigenic regions are not tightly linked to the
| protiens receptor binding function thus may vary at a greater
| rate than the RBD regions
| alevskaya wrote:
| This isn't correct. The constraints placed upon epitopes by
| the cell receptor vs antibodies aren't the same. Rhinoviruses
| and Influenza viruses escape past immunity without
| fundamentally altering their biology all the time! The 2nd
| paper cited does in fact show functional virus with a charge-
| shifting E->K mutation in its receptor binding domain that
| escape many antibodies raised against earlier strains. I used
| to engineer viruses and human immune cells for a living -
| maybe read a little more virology/immunology.
| mvanaltvorst wrote:
| Say that Pfizer were able to simulate 50 possible mutations and
| put all of them into a single vaccine, would there be any risk
| that the antibodies could interact with each other in some way
| that makes the vaccines less effective?
|
| Also another scenario: say that we get yearly Covid shots that
| contain the latest strains, would these accumulate over the
| years and start interacting with each other?
| Retric wrote:
| As I understand it, the second isn't an issue so 50 vaccines
| over 50 years would be fine, that's how seasonal flu vaccines
| are done.
|
| The first is mostly a question of how similar they are. Best
| case original vaccine covers all strains without
| modification, worst case you need 50 different vaccines. But
| the most likely combination is a mix where you might need say
| 5 vaccines, each of which over an overlapping subset of the
| 50 strains to various degrees of effectiveness.
| danarmak wrote:
| The immune system presumably has a limited capacity of
| circulating antibodies. By introducing new antibodies, do
| we reduce the amount of previous antibodies, and does this
| reduce their immune response? Is there a concept or metric
| of "antibody dilution"?
| Retric wrote:
| Antibody production ramps up and down rapidly, it's
| memory cells that get altered by vaccines.
| https://en.wikipedia.org/wiki/Immunological_memory
|
| That said the immune system is extremely complex, but
| here is a simplified version, which gives a reasonable
| overview: https://microbenotes.com/cells-of-the-immune-
| system/
| dannyw wrote:
| While correlation is not causation, I find it interesting
| that the human immune system only remembers the common
| cold and seasonal influenza for several months, but
| diseases like the polio for much longer.
|
| https://biology.stackexchange.com/a/21802
| TylerE wrote:
| "The common cold" is a loose nebula of hundreds of
| different, unrelated, virus strains. They're not even all
| the same TYPE of virus.
| ksk wrote:
| The pfizer vaccine also elicits T Cell response/cell mediated
| immunity. I'm guessing there are a few more studies in the
| pipeline..
| williesleg wrote:
| Calm down, it's a cold virus.
| qwerty456127 wrote:
| Does this suggest that immunity against some ordinary old
| pre-2019 coronaviruses also applies against the current strains?
| zaroth wrote:
| There is clearly something that prevents certain people
| (particularly kids) from contracting COVID to the point where
| they will not test PCR positive even if they are heavily
| exposed and have not had it before.
|
| I know several families in my town who have gotten COVID. All
| of these families had 2 or more kids and in 3 of the families
| there was at least one kid who never had any symptoms and never
| tested positive despite being PCR tested repeatedly.
|
| It's theorized that there is some cross-immunity that some
| people have from other coronaviruses.
| [deleted]
| TylerE wrote:
| No.
|
| Coronavirus is a generic term for a type of virus.
|
| For example, a few of the more common strains of the common
| cold, representing perhaps 15% of cases, are coronavirus - but
| they have no real relation to _the_ coronavirus, as term is
| typically used.
| qwerty456127 wrote:
| That's what I meant.
| nradov wrote:
| It depends what you mean by real relation. Both OC43 and HKU1
| are betacoronaviruses, in the same genera as SARS-CoV-2. So
| they're genetically very similar, but there's no reliable
| evidence of significant cross immunity.
| bpodgursky wrote:
| There is some anecdotal evidence of prior immunity, but is
| tangental to this development.
| Capira wrote:
| I hope it isn't mandatory?
| jerzyt wrote:
| >>> appears effective I'm not knocking the vaccine, but that's a
| pretty low scientific standard. The public is so polarized that
| we have crazy conspiracy theories on one side, and complete
| acceptance with very little questioning on the other side. A
| typical drug takes about 5 years to develop and another 5-7 for
| clinical trials, and for good reasons. It takes time to discover
| side effects. This vaccine has been developed in less than a year
| from virus discovery to production. I really hope this vaccine
| works, but I can understand the skepticism.
| fsh wrote:
| This is incorrect. Vaccines take forever to develop for
| economic reasons. Big studies are very expensive, so companies
| are typically quite hesitant to move to the next step. Vaccine
| side effects are usually quite rare, so you wouldn't see them
| in a Phase-3 trial, even if you waited for decades. This is why
| any drug is studied after approval in Phase-4 trials.
| Furthermore, vaccines side effects have historically pretty
| much always shown up at most weeks after the vaccination.
| rimliu wrote:
| To develop mRNA vaccine took what, ~10 years? It's about how
| long it takes to develop the printing press vs. how long does
| it take to print a book.
| luikore wrote:
| We still need Continuous Integration/Continuous Deployment in
| vaccine development.
| jimbokun wrote:
| The question is whether or not we're confident enough to
| administer the latest vaccine variants without clinical trials.
| zaroth wrote:
| The bigger question I have is when will we be ready to
| confidently claim that the vaccine doesn't just prevent symptoms
| but also prevents spread? (Edit: at the same or nearly the same
| 95% rate)
|
| I can't see a human trial being able to show this, and contact
| tracing is overall so poor how long will we have to wait to _not_
| see a case that can be tracked back to a vaccinated individual
| before we are willing to agree that the vaccine is highly
| effective at stopping transmission?
|
| For example, by Feb 1 we will have millions of people who are
| effectively protected at least from symptoms due to vaccine. So
| e.g. by March 1, if we have no, or single digit, reported cases
| of 2-week post-jab transmission?
|
| The corollary is how durable is the effect?
|
| To fully reopen the economy you need some kind of consensus on
| where the truth lies to these two questions.
|
| I wonder if public health agencies will never really admit, but
| just the case count will start to dwindle and mitigations will
| start to lessen, without ever really coming out and admitting
| vaccinated people don't need mitigations 2-weeks-post-jab.
|
| Similar to how we've never really admitted that people who've had
| COVID are immune and can no longer spread it.
|
| I think fundamentally gov't is too afraid of having two classes
| of citizens, and mainly, that one class (the antibody negative
| class) lying that they are actually the other.
| anonytrary wrote:
| These vaccines do _not_ prevent spread! They decrease the
| probability of symptoms, and with any coronavirus, the main
| vector of spread is going to be through symptoms (coughing,
| sneezing, etc.). This means that if you are vaccinated, you
| will be less likely to spread the virus, but you must still
| wear a mask in order to protect those around you!
| mancerayder wrote:
| That intuitively doesn't make sense for the fact that
| vaccines help produce antibodies which prevent the virus from
| spreading within the body and reproducing within the body.
| The spike protein is detected as something bad, and the body
| becomes furious and destroys the whole shebang, but not
| before binding to the spike protein as well and preventing it
| from infecting cells. If there's a lower viral load in the
| body, then it reduces the chance of spread (hint, because
| viral shedding is what causes spread across people).
|
| Put away your exclamation points and have a glance at
| https://www.nytimes.com/interactive/2020/health/pfizer-
| biont...
| nradov wrote:
| Please don't spread misinformation. We don't yet have any
| reliable evidence on that one way or the other.
| anonytrary wrote:
| This is not true, the Pfizer vaccine does not prevent you
| from carrying the virus and spreading it to others who do
| not have the vaccine. This is what a medical professional
| told me who was required to get the vaccine. Their entire
| department had to get vaccinated (Pfizer, _not_ Moderna)
| and they are still required to wear masks for this very
| reason. Do your research.
| enchiridion wrote:
| Your tone is somewhat hostile.
|
| As far as I can tell, we just don't know yet. Until we
| know, some preventative measures would be prudent.
|
| So yes, the scenario you layout is possible. However, it
| is also possible that it does stop spread.
| anonytrary wrote:
| Even if it's unknown, my advice is still the correct
| advice, and this is what is recommended by medical
| professionals. Wear a mask after you got the vaccine.
| Nabati wrote:
| > is what a medical professional told me.
|
| > Do your research.
|
| I don't mean this abrasively but, referring to an unknown
| third party for credibility and then telling people to do
| their research does not seem overly convincing to me.
| anonytrary wrote:
| Is my conclusion wrong? Best to err on the side of
| caution -- wear a mask, even if you got the vaccine.
| Period.
| feanaro wrote:
| This is the right conclusion, but for the wrong reasons.
| A vaccine which induces antibodies should prevent spread
| because it will prevent your body from producing large
| quantities of the virus and hence prevent viral shedding.
|
| The remaining factors which still require masks are the
| non-perfect efficiency (~5% of people will still get it),
| social factors (related to creating two classes of
| people; the immune and non-immune) and perhaps some
| others I forgot.
| sokoloff wrote:
| While I think I agree with you high-level, you and GP may
| be talking past each other when you use "prevent" when
| you more precisely mean "dramatically reduce [possibly to
| the point where you _effectively_ prevent]".
| feanaro wrote:
| You're right. I also just found out about research
| (mentioned somewhere downthread) on differences between
| antibody expression in different tissue types (some IgA
| subtypes predominantly found in mucosa while other IgG
| types being dominantly systemic and/or in the lower
| respiratory system). The discussion there is on a whole
| other level of precision and points toward a mechanism
| which might indeed make it possible for vaccinated people
| to transmit the disease with some degree so it's not
| quite as clear cut as I presented it.
|
| Though, intuitively, I'd still bet that vaccination will
| reduce viral shedding and the total load shedded, thus
| also reducing transmission.
| netsec_burn wrote:
| Why do you say not Moderna? Are they not equally
| effective?
| zwily wrote:
| You cannot say definitively "this is not true". The
| advice to wear a mask after vaccination is still the best
| advice with the data we have, but you made a statement of
| fact that is currently unknown.
| NiekvdMaas wrote:
| Source? This is ongoing research but the hypothesis is that
| vaccinated people spread the same rate as asymptonic
| COVID-19 carriers.
|
| For example: https://globalnews-
| ca.cdn.ampproject.org/v/s/globalnews.ca/n...
| anonytrary wrote:
| Your link 404'd for me. Here is the direct link:
| https://globalnews.ca/news/7559408/health-matters-
| covid-19-v...
|
| As I said, my contacts in the medical field have the same
| opinion as the article. It's "unknown" officially, but
| apparently people on HN don't know anyone in the field
| who is literally on the front lines researching this. The
| overwhelming opinion (articles aren't being written yet,
| expect some in a few weeks) is that the Pfizer vaccine
| does not actually prevent spread of the virus, _only
| symptoms_ which decreases the probability of spread, but
| does not completely prevent spread.
| prox wrote:
| The right term would be sterilization vaccine, at least
| thats what a epidemiologist recently called it, if I
| remember the term correctly?
| ro-_-b wrote:
| So for the vaccination it seems that:
|
| _It does not prevent the virus from spreading_ It does
| not protect against certain variations that we are seeing
| like in South Africa
|
| This means that the pandemic will still be there next
| winter some how. Likely not as bad as it is now. But it
| won't be over yet as a thread for societies. Remember
| most emerging/developing countries are not expected to
| receive vaccinations any time soon.
|
| They'll be able to update the vaccination but many people
| will lose trust in them unfortunately
|
| Means that our economies & currencies will be in trouble
|
| Remote work will break through. After 2 years nobody is
| used to anything else anymore
|
| Many people will permanently lose their job/business, but
| software companies will continue to do extremely well
| (although there will be some regulatory crack down on the
| largest companies)
| frabcus wrote:
| Another option would be for Europe and the US to get
| people from Asia and Australia/NZ to teach us how to
| track and trace.
| morsch wrote:
| The article is asking the wrong question ( _Immune but
| infectious: Can someone vaccinated against COVID-19 still
| spread the virus?_ ). The question is not whether or not,
| but to which degree. That is, how likely are they to
| spread the disease, how many people do they infect on
| average, how much virus do they shed...
| JamesBarney wrote:
| Source?
|
| Most other vaccines prevent spread. Why don't these?
| zkms wrote:
| tl;dr per this Nature article, there's different type of
| antibody responses, intramuscular vaccines are better at
| inducing the flavor of antibody that works in the lower
| respiratory tract (which is excellent at attenuating
| disease severity) but not the kind that works in the upper
| respiratory tract. Also afaict, sars 2.0 reproduces in the
| upper respiratory tract, and it's this type of reproduction
| that allows for disease spread.
|
| i'm not a virologist nor an immunologist but this is my
| understanding of the situation.
|
| https://www.nature.com/articles/s41586-020-2798-3
|
| > it is important to note that natural infection induces
| both mucosal antibody responses (secretory immunoglobulin A
| (IgA)) and systemic antibody responses (IgG). The upper
| respiratory tract is thought to be mainly protected by
| secretory IgA, whereas the lower respiratory tract is
| thought to be mainly protected by IgG27,28,29. Vaccines
| that are administered intramuscularly or intradermally
| induce mainly IgG, and no secretory IgA30. It is therefore
| possible that most vaccines currently in development induce
| disease-preventing or disease-attenuating immunity, but not
| necessarily sterilizing immunity (Fig. 2).
|
| > The lower human respiratory tract is thought to be mostly
| protected by IgG (IgG1 is most prevalent), the main type of
| antibody in serum, which is transported into the lung. The
| upper respiratory tract is thought to be mostly protected
| by secretory IgA1 (sIgA1). a, Natural infection with
| respiratory viruses induces both a systemic immune
| response, dominated by IgG1, as well as a mucosal immune
| response in the upper respiratory tract that is dominated
| by sIgA1. This process can lead to sterilizing immunity for
| many respiratory viruses. b, Intramuscular or intradermal
| vaccination leads in many cases to a strong induction of
| serum IgG but not to an induction of mucosal IgA. Although
| some IgG can also be found on the mucosal surfaces of the
| upper respiratory tract, the lack of sIgA often leaves an
| individual vulnerable to infection of the upper respiratory
| tract. c, Intranasal vaccination can efficiently induce
| mucosal antibody responses, thereby potentially providing
| sterilizing immunity in the upper respiratory tract.
| However, systemic immune responses are often lower after
| this type of vaccination. Currently, all SARS-CoV-2 vaccine
| candidates in clinical development are administered
| intramuscularly, and very few of the more than 180 vaccine
| candidates in development are designed to induce mucosal
| immunity. Although mucosal immunity might not be required
| to protect from severe or even symptomatic disease, it
| could be required to achieve optimal protection from
| infection and onward transmission of SARS-CoV-2.
| raducu wrote:
| How about intranasal flu vaccines?
|
| If we developed intranasal covid vaccines, would those
| also produce IgA antibodies?
| Exmoor wrote:
| It's been covered well in other comments, so read the whole
| thread, but basically it's expected that the vaccine would
| greatly decrease your ability to spread if not completely
| eliminate it. It's just pending hard data which is a bit
| complicated to study.
| toast0 wrote:
| None of the data you'd need to have policies based on
| calculated immunity is going to come quickly, if at all.
|
| I don't think it's reasonable to try to run an open economy for
| those who are likely immune and a parallel economy for those
| who are unknown. There's no way anyone can verify any of that
| in a day to day setting.
|
| I would expect that some international borders might reduce
| quarantine requirements if you can show evidence of probable
| immunity, but not right away.
| nradov wrote:
| Reopening the economy or not is a political choice and doesn't
| necessarily depend on vaccine effectiveness. The economy in
| Florida has been pretty much open since September. We can argue
| about whether that is wise but the reality is they are open
| today.
| elicash wrote:
| There's truth to this, but it's more complicated. In my
| neighborhood, even if our mayor "opened" things back up, very
| few would be willing to, say, dine indoors. I can say this
| confidently because we were less locked down in the late
| summer.
|
| It's not just a political choice.
| bzb6 wrote:
| Are you sure of this? Here every time restrictions are
| lifted all restaurants are crowded the very same day.
| fsflover wrote:
| The question was not about wrong political choices, but about
| the right ones.
| newsclues wrote:
| But how do you evaluate right?
|
| Public health, economic, liberty, community cohesion?
| fsflover wrote:
| Those compatible with the scientific research.
| sonotmyname wrote:
| Which scientific research? That which only takes the
| virus related deaths into account, or that which balances
| other factors such as depression, suicide, substance and
| spousal abuse, and long term economic factors?
| iso1210 wrote:
| Israel has managed to give the first shot to 20% of its
| population, and at this rate will be into herd immunity
| territory by the end of the month.
|
| As far as pressures on healthcare systems though, once over 65s
| have been vaccinated (and the northern winter ends) the
| pressures pretty much vanish.
|
| > Similar to how we've never really admitted that people who've
| had COVID are immune and can no longer spread it.
|
| Well we don't know that. In many cases the virus reproduces and
| spreads without any symptoms. If the spread occurs before the
| immune system kicks in you could still be a carrier even though
| the vaccine makes your symptoms pretty much zero.
| zaroth wrote:
| > _Well we don 't know that. In many cases the virus
| reproduces and spreads without any symptoms._
|
| We know that asymptomatic people who are not immune can
| possibly spread the virus. But that's a slightly different
| question.
|
| We know that it's very rare for someone with antibodies to be
| symptomatically reinfected with COVID. That's also a slightly
| different question.
|
| The specific question on the likelihood of someone with
| natural immunity to be able to later _spread_ COVID without a
| symptomatic infection;
|
| I've never heard of a single confirmed case of this
| happening. And the point is not that it _never_ happens, the
| point is it's a negligible risk. Smaller than, for example,
| someone who isn't immune who is wearing a mask.
|
| But from a public policy perspective, we'll never actually
| admit this, just because the second order effects -- where
| some people can rightfully walk around without a mask and are
| rightfully not subject to mitigations and lockdowns - are
| political untenable.
| selimthegrim wrote:
| Well more the idea that immunity passports bring back
| memories of really bad old societal sequelae from the
| yellow fever days
| iso1210 wrote:
| Yellow fever days? You mean before international travel
| mostly stopped?
|
| I have to show my yellow piece of paper with the stamp
| from my jab when I travel to several countries, most
| recently Nigeria
| selimthegrim wrote:
| In antebellum New Orleans, people would often try to get
| infected with yellow fever as soon as they got here to
| get it over with so if they survived they could claim
| immunity.
| Aachen wrote:
| "once winter ends" I've been wondering about that. In June
| things were just great, but at the same time our health
| agency (RIVM) claims COVID-19 is not affected by seasons. Are
| they lying (since they're saying "is not" instead of "might
| not" / "unknown"), or was what happened around June a
| coincidence?
| gomjabbar wrote:
| Hello from summer in Australia right now
| GuB-42 wrote:
| I can't believe it is not a bit seasonal, whatever the
| reason is.
|
| First wave ended in June in the northern hemisphere and
| started in the southern hemisphere at about the same time.
| We are seeing a similar shift in the second wave.
|
| It can be a coincidence but since people are more likely to
| stay inside when it is cold outside, and transmission is
| more likely inside, it makes sense.
| hutzlibu wrote:
| "It can be a coincidence"
|
| Since the cold season is usually when it is cold outside,
| yeah. Might be more than coincidence.
| iso1210 wrote:
| More non-covid hospital pressure in winter. More people
| inside.
| graeme wrote:
| On what basis are they saying it? Every single other
| coronavirus is seasonal, so I don't see why this one
| wouldn't be.
|
| Have a look at hcov's seasonality in figure 2 here:
| https://www.annualreviews.org/doi/10.1146/annurev-
| virology-0...
|
| "It's not seasonal" is one of the mantras health agencies
| repeated in february, along with "masks aren't shown to
| work" and "it doesn't" spread by aerosol.
|
| My guess is your health agency simply hasn't re-examined
| their beliefs as evidence came in.
| maxerickson wrote:
| From the phase 3 trials you'd absolutely expect cases to occur
| after vaccinations. That's what the 95% efficacy after 2 doses
| means, that 5% of people had symptomatic infections.
|
| Hopefully it is the case that the 5% are people that have a
| weak response to the vaccine and the remainder mostly aren't
| infectious. They can study this by monitoring for asymptomatic
| infections (I don't know if they are going to or not).
| doktorhladnjak wrote:
| 95% effectiveness does not mean 5% of people had symptomatic
| infections. It means there were 20 times more infections in
| the placebo group compared to control.
|
| If you gave the vaccine to 1000 people and placebo to 1000
| people, and 100 of the placebo and 5 of the treatment group
| got sick, that's 95% effective, as is if all 1000 in the
| control group got COVID and only 50 in the treatment group.
| maxerickson wrote:
| Yep, thanks for clarifying.
| TheGallopedHigh wrote:
| You're saying the same thing as the parent comment.
| dtech wrote:
| Parent said 5% had symptomatic infections, 50 in this
| example, while the correct number is 0.5% percent or 5
| people.
| GistNoesis wrote:
| What worries me is that there doesn't seem to be some global
| coordination in the distribution of the vaccines. It looks more
| like an individual race, than a synchronized collective effort.
|
| In the scenario where only the old accept to get vaccinated, and
| the vaccine doesn't reach the required threshold to stomp the
| virus. The virus become manageable, the economy reopen but the
| virus run rampant in the asymptotic population slowly mutating
| over-time until it finds a variant that is resistant to the
| vaccine by successfully infecting a vaccinated person.
|
| And it just needs for this to happen in a large population
| cluster where the vaccination doesn't reach the threshold, either
| because they do not have access to the vaccine yet or because
| some fraction of the population decide to not get vaccinated, for
| everyone to get screwed-up again.
|
| Then we get a new vaccine every year.
| Thorentis wrote:
| Congratulations, you discovered the flu.
| GistNoesis wrote:
| Touche ! What is so sad is that it can still be avoided.
|
| But the current situation where we simultaneously have a high
| number of active case and high number of vaccinated people
| over a sufficiently long time because of slow vaccination
| schedule, is a recipe for creating vaccine resistant
| variants.
|
| As soon as we start vaccinating we are giving the virus
| opportunities to pressure-select against the vaccine. The
| more active case we have and the longer it takes the better
| for the virus.
|
| I'm no epidemiologist, but with the apparition in a short
| amount of time of 2 variants which affects the spike protein,
| it seems the current level of active case we are entering a
| red-zone, where the virus is given too many opportunities to
| mutate. And we should try to contain it via the current
| measures (masks, tracking and lock-downs), before sabotaging
| our best card.
| [deleted]
| m3kw9 wrote:
| How effective is it to use one of those molecular simulation
| tools to quickly calculate if the antigens created still have
| high affinity to bind to the mutated spike?
| corona-research wrote:
| Does the vaccine cure hypochondria?
| anonthinker wrote:
| I know some of you are following this closely and I have some
| questions I haven't seen any proper answer. I am hoping one of
| you can shine some light.
|
| How long will the mod-RNA express the spike proteins? (where is
| the actual 'protein expression'/time plot?)
|
| The poly(A) tail isn't just A (which would give a mechanic answer
| to my first question?), there is also a 10-nucleotide linker
| (GCAPsAPsGACPs). I wonder if this could be there to trigger some
| sort of self-amplification. Can someone point me to the relevant
| paper?
| jakub_jo wrote:
| It's not the "Pfizer" vaccine. It's either the "Biontech" vaccine
| or the "Biontech/Pfizer" vaccine. Please fix the title.
| mseidl wrote:
| AFAIK, Biontech developed the vaccine and had successful tests
| in mice/monkeys, then they asked Pfizer help for bigger scaled
| testing/manufacturing?
| jonplackett wrote:
| Pfizer have said it will only take a few weeks to tweak their Rna
| vaccine, if it does need to be changed.
|
| Anyone know how long it would take AstraZeneca with a more
| traditional vaccine?
| libertine wrote:
| The problem is that we're turning this into a cat and mouse -
| Pfizer has nowhere near the capacity to ramp up production to
| make a positive impact after all.
|
| If we enter a cycle of new variants every 9-6 months that
| require new vacines, simply because the volume of people infect
| allows the virus to have enough diversity, then it's pointless.
|
| It's basically a "weird flex" from Pfizer, because what they
| should say is: even though we can make a new vaccine easily, we
| will have nowhere near the production capacity to make a
| difference, so global governments need to get their shit
| together.
| iguy wrote:
| Manufacturing capacity is going to be a big constraint this
| year, but surely whatever factory was going to make the old
| variant, could equally well make some new variant of the
| vaccine.
|
| Longer-term, if we need a new vaccine every 9 months, that
| doesn't sound like a huge manufacturing problem. We
| manufacture many high-tech things on a scale of 1 per person
| per year, like the flu vaccine. The difficulty is ramping up
| fast (especially when you think that demand may only last a
| year).
| libertine wrote:
| It's the whole chain, manufacturing is just a portion of it
| - the logistics required for this vacine, and the volume of
| people that needs to be vaccinated.
| iguy wrote:
| Sure, and the logic is pretty similar for the whole
| chain.
| bluGill wrote:
| Pfizer can develop more capacity if they see a need. Right
| now it isn't looking useful, as several other competitors are
| expected to be approved in the near future before they can
| bring more production online. If they need to develop a new
| vaccine every few months, the speed they can make new
| variations would make more investment in manufacturing worth
| it.
| phreeza wrote:
| Will a tweaked vaccine have to go through the full approval
| process again?
| lame-robot-hoax wrote:
| I believe only phase 1 and phase 2.
| jonplackett wrote:
| How long do phase 1/2 take?
|
| I wonder if, under some potential circumstances (eg. the
| virus turns out to escape current vaccine & be much more
| contagious) exceptions will be made.
| bluGill wrote:
| A few months. Though we don't have enough understanding
| of mRNA to skip phase 3 yet. That dull take time. How
| much time is a question of tradeoffs.
| iridium_core wrote:
| Is there any evidence that this new 'variant' has any impact to
| infectiousness or death?
|
| Or is it simply genetic drift?
| avl999 wrote:
| No evidence that it is deadlier than other variants. Some
| evidence that it is more infectious.
| sbinthree wrote:
| It's been rapidly becoming the dominant variant in places
| with various different kinds of measures so I think it's for
| sure more infectious at this point.
| iridium_core wrote:
| So incessant, and seemingly ineffective, lockdowns have
| succeeded - in selecting for a variant of COVID which is
| resistant to lockdown? What biological or physical
| mechanism could allow it to spread more than the original?
| sbinthree wrote:
| Yes
| wwweston wrote:
| On one hand, it may be plausible that taking any measure
| that makes it harder to spread... favors a variant that
| can spread more easily.
|
| On the other hand, spreading more easily means higher
| reproductive fitness under _any_ circumstance. And _not_
| taking measures to reduce spread probably just means more
| infections faster, which is more opportunity for
| reproduction and mutation, which means you probably get
| higher fitness variations sooner.
|
| Also I'm trying to think of anywhere in US/UK society for
| which "incessant lockdown" could possibly be an accurate
| description of policy much less behavior.
| nmca wrote:
| Imperial study was in the context of a tiered UK system
| that keeps schools, so increased infection from young
| people _is my personal and ill-informed_ hypothesis of
| how the new variant achieved 50-70% increased r0 under
| restrictions.
| JamesBarney wrote:
| Just a reminder that greater infectiousness is worse than
| greater lethality.
|
| Say you have two variants, variant S-spreader and variant
| L-lethal. S kills 1 in 100 people and has a doubling time of
| 3.5 days L kills 2 in 100 people and has a doubling time of a
| week.
|
| First week L kills twice as many people of S. Week 2 they
| kill the same number of people. Week 3 S kills twice as many
| people as L Week 4 S kills 4x as many people as L.
| lazyjones wrote:
| This is plain wrong. You have 2 variables there and can't
| claim that one has greater effect based on 2 examples. It
| can be refuted by a suitably chosen 3rd example, e.g.
| N-nonlethal kills 1 in 10000000000000 people and has a
| doubling time of 1 day.
| fpgaminer wrote:
| It should be noted that increased infectiousness will
| inherently result in a larger number of deaths, even if it is
| not "deadlier". i.e. the new strain may still only be fatal
| in 0.5% of cases, but if it infects more people that's more
| rolls of the dice. The original strain was only projected to
| infect 60-70% of the population (if left unchecked). A new
| strain being 70% more infectious drastically changes that
| figure.
|
| Not to mention a similar uptick in serious cases and even
| just more people presenting to the hospital. Imagine the
| current situation, where some cities are already at 0%
| capacity, but 70% worse...
|
| Just something worth noting when we say that a new strain is
| _just_ more infectious.
| Erlich_Bachman wrote:
| Yep, but at the same time if they would have said that it
| is "more infectious and more deadly" - that would have even
| more incorrect (without clarification), given that those
| terms usually refer to specific properties.
| lazyjones wrote:
| > _It should be noted that increased infectiousness will
| inherently result in a larger number of deaths, even if it
| is not "deadlier"._
|
| That's wrong if this virus, like many other viruses, is
| mutating to become simultaneously more infectious and less
| lethal.
|
| https://www.reuters.com/article/us-health-coronavirus-
| mutati...
| graeme wrote:
| Actually it isn't wrong. A 70% increase in an
| _exponential_ gain leads to many multiples more cases.
|
| You could halve the death rate in that scenario and still
| have 10x the number of deaths or more.
|
| Run two exponential series: one at 1.1x, one at 1.7x.
| Start at 1,000 cases each. Death rate 1% for the first,
| 0.5% for the second. Assume doubling in a week. Check new
| cases and thus new deaths after eight weeks.
|
| 2143 new cases on week eight fir the second one, 21.4
| deaths.
|
| 110,199 new cases on week eight for second one, resulting
| in 550.5 deaths.
|
| 20x worse. And unfortunately the new strain doesn't seem
| to be less deadly, so it would be 40x worse if death rate
| the same.
| lazyjones wrote:
| You are wrong on principle because you stopped thinking
| after you calculated the death rate after week eight. The
| virus doesn't stop spreading in either of the
| hypothetical cases and the population is a finite number.
| Keep calculating!
|
| Also, your numbers are arbitrarily picked. Why don't you
| pick 1.8x and 1% vs. 1.9x and 0.999%?
| graeme wrote:
| Because 1.1x is about the r pre-existing restrictions had
| most western societies at. And it's estimated the new
| variant is 70% more transmissible.
|
| >You are wrong on principle because you stopped thinking
| after you calculated the death rate after week eight. The
| virus doesn't stop spreading in either of the
| hypothetical cases and the population is a finite number.
| Keep calculating!
|
| This only applies if the plan was to let literally
| everyone get infected. That wasn't the plan. We have
| vaccines now. It should be possible to end things by the
| end of summer, so excess deaths now are needless deaths.
|
| Also you're ignoring speed. 200,000 hospitalizations in a
| week is much much worse than 200,000 in a year. Get too
| many people needing to be hospitalized at once and the
| death rate goes up because you can't treat them as well.
| You also get more deaths from other conditions as
| hospitals can no longer serve cancer patients, heart
| attack victims past a certain point etc.
| lazyjones wrote:
| You keep introducing more variables and more arbitrary
| numbers, we won't get to agree on anything this way.
|
| It's well known that harmless viruses exist, they infect
| a lot of people and kill nobody (or almost nobody).
| Claiming that more infectious = generally more lethal is
| just not based on facts. If Covid-19 mutates into a
| mostly harmless variant, we will easily treat the few
| more severe infections and nobody will die.
| graeme wrote:
| > You keep introducing more variables and more arbitrary
| numbers
|
| These variables are the ones that are relevant to deaths
| and have been talked about since the beginning of the
| pandemic: hospital overwhelm, total percent of populace
| infected, etc
|
| To refuse to deal with the complexities of the situation
| doesn't make them go away. I didn't introduce any factors
| apart from the common ones.
|
| > It's well known that harmless viruses exist, they
| infect a lot of people and kill nobody (or almost
| nobody).
|
| We're not talking about those viruses though. Most
| viruses that we don't have a vaccine for are either
| orders of magnitude less lethal or substantially less
| contagious.
|
| > Claiming that more infectious = generally more lethal
| is just not based on facts.
|
| I didn't say that. I said that at the level of lethality
| coronavirus is at, an increase in contagiousness is worse
| than an increase in lethality. Very different claim.
|
| > If Covid-19 mutates into a mostly harmless variant, we
| will easily treat the few more severe infections and
| nobody will die.
|
| This would be true if it mutated into something maybe
| 100x less contagious. An entirely theoretical
| possibility. That's how much more lethal covid is
| compared to stuff like the cold.
| maxerickson wrote:
| What does 'evidence' mean in the question?
|
| There is certainly something going on in the UK and Ireland,
| but it's not a randomized controlled study designed to measure
| the infectiousness of the variants that have recently been
| sampled there.
|
| (because it's exponential, higher infectiousness can be quite a
| lot worse than higher lethality)
| graeme wrote:
| Yes. Denmark has studied it and the new variant is doubling its
| prevalence in denmark every week too.
| aqme28 wrote:
| The British variant is estimated to be about 40-70% more
| infectious, which is pretty bad of course.
|
| https://www.who.int/csr/don/21-december-2020-sars-cov2-varia...
| elij wrote:
| https://www.imperial.ac.uk/mrc-global-infectious-disease-ana...
|
| It's very important, specifically in the UK, to put N501Y in
| the context of political decisions that impact the R index.
|
| https://twitter.com/dgurdasani1/status/1344774576371335175
| JamesBarney wrote:
| There is. In the UK you are seeing a huge spike in infections
| at the same time the percentage of coronaviruses attributed to
| the new variant sky rocket.
|
| Look here for how one of the lines is not like the others. (UK)
|
| https://ourworldindata.org/coronavirus-data-explorer?zoomToS...
| ashtonkem wrote:
| Oh yes, pandemic. I feel like I was forgetting something.
|
| That's good news at least.
| johndoe42377 wrote:
| Why should it be not? It will be effective as long as the core
| protein against which the immune system response is to be
| triggered will remain the same.
| lrossi wrote:
| This is like saying that your input schema has changed a
| little, but you still want to push the code to production
| without retesting it.
| rimliu wrote:
| It is nothing like that.
| UltimateBallR wrote:
| Extremely good news!
| PurpleFoxy wrote:
| What worries me is the chance that we will see another super
| virus in a few years except one country already has vaccines
| developed on day one and will not share the information on them.
| duxup wrote:
| I feel like in this economically connected world, that would be
| a sort of global politics suicide. It would be one of the few
| acts that would likely galvanize... everyone. The leaders of
| those nations would be pariahs in a way that even a nation like
| N. Korea is not.
|
| For the nation's without a vaccine, the leaders there likely
| would be quite motivated to act and enjoy a great deal of
| support at home.
| ggm wrote:
| Remember China and the USA were in a full bore trade war and
| despite some mud flinging and half-truths,essentially the
| global health system was kept informed.
|
| The genome was shared. At least four competitors in global
| economic terms (China, Russia, the EU and the USA) all
| developed vaccines.
|
| This is not like pre-hydrogen bomb information hoarding. The
| techniques behind mRNA are taught worldwide. Most medicines
| come from India, which was a leading non-aligned economy for
| years and years.
| bluGill wrote:
| In general sharing vaccine information with your enemy is
| considered a good thing by generals. No good army wants to
| get involved in biological warfare at this time as it is too
| risky as to turning against you.
|
| The above does leave room for bad armies. Some tiny
| insignificant nation might do this. China isn't
| insignificant, and not stupid. Even in an all out war they
| would still share virus and vaccine information with their
| enemies as there is nothing to lose and goodwill to gain.
| f430 wrote:
| As long as it's not a communist country then we are fine.
|
| They still not letting WHO scientists into Wuhan to study it's
| origins and we are being told to take CCP's word at face value.
| JamesBarney wrote:
| Developing vaccines are easy. The cost is all testing. Other
| countries could easily reverse engineer the vaccine and make
| it.
| newsbinator wrote:
| That's part of the reason every major country in the world has
| a well-funded department of espionage.
| zelly wrote:
| Why does the vaccine for SARS-CoV-2 work so well but there was no
| vaccine at all and still isn't for SARS?
| CorrectHorseBat wrote:
| Hard to test the efficacy of a vaccine on an eradicated
| disease.
| hobofan wrote:
| Because mRNA tech for rapid vaccine development wasn't
| available back then and it didn't spread so far that there was
| political pressure for expedited trials. Now it is eradicated
| anyway.
| QuesnayJr wrote:
| Part of why these vaccines were developed so quickly is that
| much of the preliminary work was done for SARS.
| bluGill wrote:
| The is/was several SARS vaccines. They never got to phase 3
| trials, because of various problems. We learned enough from
| them to skip all the issues this time around.
| meekmockmook wrote:
| Another social media panic for no reason. Big Tech is the
| ultimate superspreader.
| [deleted]
| eclipxe wrote:
| Nope, you are incorrect.
| meekmockmook wrote:
| The vaccine works on the new variants. The variant spreads
| faster than previous ones, but in the end the rules don't
| change: Wear a mask, wash your hands, don't go inside with
| people if possible.
|
| People were sharing on a Facebook and tweeting that the new
| strain was being spread through touching surfaces and farts
| and that masks no longer work.
|
| Big Tech is poison and many thousands would still be alive
| today if they had never logged on. These companies are no
| longer defensible.
| SpicyLemonZest wrote:
| The problem is that, because the variant spreads faster
| than previous ones, rules which were sufficient to keep
| previous ones in check will likely be insufficient to keep
| the new one in check. We'll have to get stricter about the
| rules, get vaccine rollout accelerated quite a bit, or find
| ways to handle a lot more disease than currently exists. I
| have no doubt some people shared weird falsehoods about it,
| but there's still a true reason for concern.
| corona-research wrote:
| Lol
| meekmockmook wrote:
| Speaking from California, the only change we could make
| is convincing law enforcement to enforce the rules (they
| won't) and changing the bizarre vaccine restrictions that
| are leaving 75 percent of our doses in a freezer while
| thousands who are offered it say no thanks.
|
| A massive percentage of the public has decided to give up
| on safety protocols and if Thanksgiving and Christmas
| didn't change any minds, why would this?
|
| What good did terrorizing the people who are already
| following the rules with this variant panic do? "THE
| VACCINE MIGHT NOT WORK NOW!" only scares people who want
| the vaccine. The media frenzy around the variant did
| absolutely no good.
| SpicyLemonZest wrote:
| What you're saying is probably true. But I don't think
| the media should refrain from reporting true, relevant
| information just because they don't think it will do any
| good if it's known.
| meekmockmook wrote:
| Oh, of course news should be reported. But a week
| straight of panic mongering headlines? That does people a
| disservice and spreads fear for $. Big Tech and corporate
| media have a profit incentive in spreading terror.
| SpicyLemonZest wrote:
| Fair, I certainly can't endorse a lot of the headlines
| I've seen. Headlines are just very bad and we as a
| society have got to find a way to fix them.
| wwweston wrote:
| What's bizarre about the vaccine restrictions? The
| publicized plans I'm aware of start with healthcare
| workers and long-term care residents, which is pretty
| much what I expected. I've heard there are about 3
| million of those people and 1 million doses, so even if
| over half of those people for some reason are refusing
| doses, there's no reasons to expect that we're through
| that crowd yet.
|
| I've got several acquaintances who work in both areas and
| what I'm hearing that there _are_ challenges: not ones
| that have to do with "rules", but actual supply and
| logistics. Still, among these are people who've received
| their first dose.
| meekmockmook wrote:
| There's been a serious problem im CA with Healthcare
| workers rejecting vaccines which are then either
| discarded or put away in a freezer. Only 25 percent of
| the supply has been used, including the ones reserved for
| dose 2.
| jeofken wrote:
| Any CA health care worker on HN? Why do most of you
| reject these vaccines?
| syspec wrote:
| Many of them simply do not want to be "the first ones to
| get this untested vaccine".
|
| That is the consensus, and even within medical community
| misinformation about the vaccine has footing.
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