[HN Gopher] Sputnik V vaccine-neutralization escape by SARS-CoV-...
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Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike
variants
Author : pabo
Score : 59 points
Date : 2021-04-04 14:25 UTC (8 hours ago)
(HTM) web link (www.medrxiv.org)
(TXT) w3m dump (www.medrxiv.org)
| phreack wrote:
| The president of Argentina has just been diagnosed with Covid,
| with mild symptoms, after being vaccinated with both doses of
| Sputnik for over a month or two.
| m0llusk wrote:
| There is speculation that Argentina may have failed to keep
| Sputnik V cold enough during distribution, so it is quite
| possible that the president and others recently vaccinated
| received degraded vaccine.
| mromanuk wrote:
| No, that's just speculation or fake news [1]: the Sputnik V
| boxes can last up to 60hs without refrigeration
|
| 1: https://factual.afp.com/las-cajas-con-vacunas-sputnik-v-
| mant...
| mrkramer wrote:
| So how we should know is vaccine good or is it degraded? Any
| way of testing?
|
| Not all batches should or could be tested but you could do
| random sample testing.
| sz4kerto wrote:
| Completely expected. That's why the efficacy is not 100%.
|
| We have people in hospital after 2 rounds of Pfizer.
| ainar-g wrote:
| > [...], we determined that 8 out of 12 (75%) of serum samples
| from 12 recipients [...] showed dose response curve slopes
| indicative of failure to neutralize rcVSV-CoV2-S: B.1.351.
|
| I may be misreading this, as English is not my native language,
| but 8/12 is 66 % and not 75 %, no? Or does the "(75 %)" refer to
| something else?
| qzw wrote:
| Off-by-one errors, they're not just for programmers anymore.
| amluto wrote:
| Someone needs to do exactly the same study (same methods, ideally
| same lab) on sera from people vaccinated with all the major
| vaccines. The lack of a valid comparison study is ridiculous.
| ObscureScience wrote:
| I wouldn't say it's ridiculous. This is generally how a
| scientific study is done. One "object" per study. An article
| like this is not made to stand alone and should in general not
| be used for non-science purposes, such as policy-making. First
| order comparative studies (such as experiments) of course
| exists, but comparisons are generally done to my knowledge in
| meta-studies.
|
| For laypeople and policy makers we of course need comparisons
| and validations before we let them guide our choices.
| nerdponx wrote:
| At this point, what is the cost-benefit of further vaccine
| development versus heavier investment in drugs and other
| therapies to reduce the severity of disease?
|
| There are a couple doctors in the US (particularly Peter
| McCullough) who make a case that we haven't invested enough in
| the latter and too much in the former. Naturally the anti-vax
| people seem to love these guys, so it's hard to find any kind of
| balanced analysis on it.
|
| Or do the numbers still work out to be "more pandemic, more full
| hospitals, many more dead" no matter how good the drug treatment
| gets?
| maxerickson wrote:
| How recent are these arguments?
|
| Deploying the vaccines is very cheap compared to
| hospitalization.
|
| And like a sibling comment has already said, we should just be
| spending money anywhere it even seems to make sense.
| kurthr wrote:
| There's lots of work on anti-virals and other drugs, but unless
| you happen to hit a pre-approved drug showing both efficacy and
| safety will take so long that it probably won't matter until
| the next epidemic. Drug treatments are much harder to develop
| without significant side-effects and also likely less effective
| than a well targeted vaccine.
|
| Watch around 1hr into this TWiV, if you're interested in what
| targets there are for anti-virals, who's working on them, and
| why they're hard.
|
| https://www.youtube.com/watch?v=7dL-ll8dSmY
| hannob wrote:
| A lot has been invested in drugs. Most of them don't work. The
| best that was found was Dexamethasone, which reduces mortality
| in severe cases significantly.
|
| Generally medication for viral infections seems to be hard.
| There isn't much good medication for other respiratory viral
| diseases. It doesn't look like a major breakthrough in drug
| treatment will happen.
|
| A vaccine can make the difference between "you get the disease"
| and "you don't get the disease and can't spread it to others".
| No drug comes remotely close to that.
| amluto wrote:
| A lot of very competent coordinated studies of drugs have
| been done. Oh wait, no it hasn't.
|
| We had a mishmash of variously competent and incompetent
| studies of AZ/HCQ. We have anecdotal data on ivermectin. We
| have some preliminary studies of fluvoxamine (excellent
| results, needs follow up); the large scale expedited follow
| up is MIA. It's been over six months from the original study
| -- there is no fundamental reason it should take more than
| two months to test it on a few tens of thousands of people.
| Ditto for anti-androgens. Camistat ought to have at least
| some effect (famous last words); this has been known for
| something like a year with no meaningful followup.
|
| What's needed here is IMO public health department
| coordination on studies, which isn't quite the same thing as
| money.
| entee wrote:
| To be clear, almost all of these studies showed very small
| effect sizes. The best therapeutics we have are remdesevir
| (small but real effect on severity, unclear effect on
| hospitalization and death), dexamethosone (moderate to
| large effect on death when hospitalized), and antibody
| drugs for which Lilly's has already been remove because
| ineffective against variants though Regeneron's cocktail
| seems quite good. Fluvoxamine is I'm sure under
| investigation, we'll get a readout eventually but that's a
| relatively new result.
|
| The best drugs we have are either:
|
| 1.) treat the virus with a novel entity (Regeneron, the
| other antibodies)
|
| 2.) treat the inflammation (dexamethosone, possibly
| eventually fluvoxamine)
|
| The repurposing and general antivirals (including
| remdesevir) have little effect and likely won't make a
| difference. There are novel drugs being developed (Pfizer
| just started a protease inhibitor trial) but that's the
| only place I'd expect to see real impact, with fluvoxamine
| as a treat the symptoms wildcard. People have been trying
| to find drugs or repurpose, and academic medical centers
| have been working on it. It's that almost nothing works
| when subjected to the hard trials.
| maxerickson wrote:
| There's likely room to pick better monoclonal antibodies
| to use. There was an antibody identified that smashed
| variants, for instance.
|
| https://www.medrxiv.org/content/10.1101/2021.01.26.212502
| 24v...
|
| Some contextualization at https://twitter.com/K_G_Anderse
| n/status/1367592606641704961
| amluto wrote:
| The cost vs benefit analysis is: do all of the above. The total
| amount spent on biotech related to Covid is negligible compared
| to the cost of Covid. Israel seems to understand this. Many
| other countries are orders of magnitude off in their analysis.
| [deleted]
| codeulike wrote:
| Most of these studies just look at antibodies (because they are
| easiest to study) but all the indications are that T-cells from
| all vaccines will continue to work well (thus preventing serious
| disease) because T-cells are much more comprehensive in their
| recognition abilities.
|
| So covid will try and evolve to keep spreading but it will become
| less deadly as vaccination and natural immunity increase. So its
| destiny is to become a cold virus like the other human
| coronaviruses.
|
| https://twitter.com/Coronavirusgoo1/status/13769286914738135...
|
| https://twitter.com/Coronavirusgoo1/status/13667086756797644...
|
| https://twitter.com/profshanecrotty/status/13552620195622092...
| __blockcipher__ wrote:
| SARS-2 was always destined to become yet another endemic
| seasonal respiratory virus, just to be clear.
|
| Also, it basically _is_ a cold virus already. For the majority
| of the population it's a mild respiratory virus. For the very
| elderly it is quite deadly. I wish more people appreciated this
| fact.
|
| Interestingly OC43, one of the already-extant human CoVs, seems
| pretty comparable in mortality for the elderly last time I
| checked.
| NicoJuicy wrote:
| 3 months ago, a friend of mine got it and he couldn't even
| walk the stairs.
|
| He's 34 and does a lot of sports. So, i wouldn't say that
| it's a cold virus already... Not deadly for younger people,
| doesn't mean it has no consequences.
| tunnuz wrote:
| As anecdotal as it can be, I also know people in their mid-
| thirties workout complicating pathologies and in good shape
| that ended up being treated in ICUs and on ventilation (one
| with a collapsed lung, pneumonia and a bacterial
| infection).
| NicoJuicy wrote:
| Well, i did mention it because it's not the only one I
| know.
|
| A friend of mine is a nurse and she also mentioned lots
| of young and fit collegues getting it pretty bad.
|
| But correct, no research. But mostly people i know they
| got infected. Sure, some have nothing or only lose smell
| and taste.
| Jeema101 wrote:
| >For the majority of the population it's a mild respiratory
| virus
|
| I know someone in her 40s who got it and is not overweight.
| She said it was terrible and that she's definitely getting
| the vaccine because she never wants to get it again.
|
| What exactly would you consider a non-mild respiratory virus?
| codeulike wrote:
| _SARS-2 was always destined to become yet another endemic
| seasonal respiratory virus, just to be clear._
|
| People were certainly saying that from the start, but lots of
| people were saying lots of things from the start. Now that we
| know that natural immunity lasts a decent while, and now that
| we know that its possible to vaccinate for it, and now that
| we know that the T-cells are going to be robust, then the
| likely future paths are becoming much clearer. One year ago,
| none of that was clear.
| somewhereoutth wrote:
| That is just speculation I'm afraid. There is much evidence
| that newer variants are more contagious, more virulent, and
| affect younger people more severely. Brazil's experience is
| instructive.
|
| Thankfully the fantastic results of the mRNA vaccines mean that
| we should be able to suppress Covid down to the levels of
| measles, if not eradicate it like smallpox.
|
| As ever we should be wary of those who seek to deny the
| seriousness of Covid, or suggest it cannot be defeated. We
| should try to understand any agenda they may have, perhaps
| including:
|
| 1. Having previously decided Covid was not serious, they are
| trying to justify their actions/lack of actions that put others
| in danger.
|
| 2. They have financial interests threatened by the necessary
| non pharmaceutical interventions.
|
| 3. Covid attitude has become a partisan political act.
|
| 4. They are influenced by certain philosophies around notions
| of 'survival of the fittest', 'culling the herd' and such like.
| devit wrote:
| How bad is this result and the similar result on the AstraZeneca
| vaccine?
|
| Does it mean that the South African variant will almost certainly
| cause another pandemic in countries vaccinated with those (thus
| requiring a revaccination with an mRNA vaccine) or is there
| somehow a chance that the variant won't be prevalent?
| throwaway4good wrote:
| I believe az had similar (bad) results which caused south
| africa to pause the rollout.
| petre wrote:
| Yup, except none of the recipients in the AZ study had severe
| cases.
| amluto wrote:
| IIRC no one in either arm of that study had a serious case.
| The study was nearly useless.
| Barrin92 wrote:
| the problem is of course that even if that's true, if the
| virus spreads asymptomatically the same mutation risk
| applies to the variant itself and at some point then we
| might up with something that again completely escapes
| immunity and vaccination.
|
| It's just evolution in action. Any variant that dodges the
| vaccine starts a new game of dice.
| throwaway4good wrote:
| I don't think it is the vaccine technology rather what part of
| the virus the vaccine causes the immune system to react on.
| newdude116 wrote:
| If I may point to a comment of mine that got heavily downvoted:
| https://news.ycombinator.com/item?id=26664839
| Kliment wrote:
| This study is not particularly interesting as a measurement of
| vaccine effectiveness (because of the extremely low sample count
| of 12 patients). So don't read too much into the particular
| numbers. Instead, there's two useful and valuable results in it:
|
| 1. It gives us information on the mechanism that the variants are
| using for vaccine evasion - the E484K substitution which was the
| suspected mechanism for B.1.351 ("south african variant") was
| tested on its own and did not evade the vaccine-induced
| antibodies as effectively as the full B.1.351 mutation set. This
| tells us that there is some other mechanism in B.1.351 that makes
| it more successful at evading antibodies. This is important and
| valuable information.
|
| 2. It demonstrates a really fast, safe, and clever method of
| testing vaccine effectiveness against a new variant - what they
| did was to take an entirely unrelated virus, graft a modified S
| protein on it, expose it to blood serum from vaccinated patients,
| and then try to infect a cell culture with it. By counting
| infected cells compared to the same count without the serum
| exposure, you can measure how effective the neutralization is,
| without having to measure infection counts in a large population.
| This is awesome and can easily be done with other vaccines and
| any new variant that shows up, as long as it's sequenced, even if
| it doesn't have much prevalence in the population. In fact, you
| can use this method to test hypothetical variants that only exist
| in animal viruses or not at all, and be able to redeploy vaccines
| that are particularly effective against those in regions where
| they happen to emerge. This, to me, is the absolute highlight of
| this paper, and I suspect it will be extremely useful.
| wrongdonf wrote:
| If the herpes virus were new, spread around the entire world and
| infected 2/3 of people and resisted all of our efforts to
| eradicate it, would we panic? Should we panic? The idea of
| coexisting with a virus is not pleasant but it wouldn't be the
| first time I guess.
| rediguanayum wrote:
| More commentary on reddit:
| https://www.reddit.com/r/COVID19/comments/milxvy/qualitative...
| It basically echoes comments here, that there's a significant
| reduction in neutralization (and paper says several instances of
| no neutralization in some sera). Comments also says that the pre-
| fusion spike stabilization used on the mRNA vaccine and J&J
| (which otherwise similar to Sputnik as both use Adenovirus
| vector) seems to be the difference.
| kurthr wrote:
| If you're interested in a fairly long discussion with the(?!)
| guy who developed the stabilized spike protein substitutions.
| Have a look at this TWiV.
| https://www.youtube.com/watch?v=P9S28_5AqUA
| abdullahkhalids wrote:
| What is the effect of taking multiple vaccines, with a few months
| of gap? Sputnik is available to me starting yesterday. If I take
| it now, will taking a different vaccine that is effective against
| the variants later on, give me immunity? Or will the new vaccines
| not do anything because the immune response has already happened?
| mensetmanusman wrote:
| No one knows, it hasn't happened before and it would probably
| be hard in the past to just test continuous vaccinations
| indefinitely.
| raducu wrote:
| The only issue could be if you take Sputnik now and Sputnik V2
| too soon, if they use the same viral vector in the future (you
| could develop antibodies to the adenovirus itself, afik Sputnik
| uses 2 adenoviruses for dose 1 and dose 2 for this exact
| reason) if the vector is different, they will both work(in the
| case of mRNA the vector is not an issue, afik).
|
| So if you're allowed to get another vaccine in a couple of
| months, take Sputnik now.
| amluto wrote:
| It's unknown. There is a phenomenon called "original antigenic
| sin" that may or may not apply.
|
| There's also a potential issue with immunity to the vector.
| kurthr wrote:
| Multiple vaccines have not been tested, but immunology suggests
| they would be safe (using the same adeno-virus would likely be
| less effective since your body would pre-empt spike
| production). One possible hypothesis for why Sputnik (which it
| self is a succession of two different adeno-virus laden spike
| protein generators) is less effective is that it (unlike
| Moderna, Pfizer, J&J) does not appear to use a stabilized Spike
| protein, which makes the immune response it generates more
| susceptible to this substitution. They key is what parts of the
| artificial vaccine spike you develop antibodies for, as to how
| effective the vaccine is for a variant since much of the active
| portion of the protein is unchanged.
|
| However, since both Moderna and Pfizer are testing mRNA
| "booster" vaccines specifically for the SA variant, you might
| just wait for that. They don't have an adeno-virus vector that
| could be pre-empted by immune response.
| randomopining wrote:
| So essentially Sputnik is most likely useless against the South
| African variant?
| monocasa wrote:
| My amateur reading of the paper: They say that there's a chance
| still it can reduce some of the symptoms and reduce the need
| for hospitalization of the South African variant (B.1.351), but
| it doesn't do a great job at preventing infections in the first
| place.
|
| > we determined that 8 out of 12 (75%) of serum samples from 12
| recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed
| dose response curve slopes indicative of failure to neutralize
| rcVSV-CoV2-S: B.1.351.
|
| > Furthermore, we acknowledge that in vivo protective efficacy
| can be derived from Fc effector functions of antibodies that
| bind but do not neutralize.
| konart wrote:
| Useless? No. Less efficient? Likely.
|
| I guess they will have to produce an updated version in nearest
| future.
| [deleted]
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