19 ms·
SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma
- KETpXDDzR 6y agoA new mutation of COVID19 has been discovered in an South African donor. With this mutation, the spike protein changed which might render all existing vaccinations less effective or even ineffective.
- cromka 6y agoFrom the article: "These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines." So it suggests that only spike-based vaccines may have reduced efficacy against it. I suppose the inactivated-virus vaccines should be fine. Which would put China and India at huge advantage (https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html https://www.nytimes.com/interactive/2020/science/coronavirus...).
- hadlock 6y agoDo you have a link, or some sort of corroborating evidence to support this statement
- eloff 6y agoThat was in the article.
- zibbity-rw 6y agoThis is the one headline I’m constantly afraid of reading... do any HN biotech experts have any comments or feedback? Is this a serious cause for concern?
- beamatronic 6y agoYou should continue to wear a mask. You should continue to social distance. You should continue to avoid congregating indoors with strangers.
- gewa 6y agoPlease note, that neutralization by antibodies is only one of the many possible ways how our immune system can take action. Antibody recognition is still possible with the found mutant: "To determine whether 501Y.V2 is still recognized by non-neutralizing antibodies, the binding of polyclonal sera (from Fig.2a) to a recombinant 501Y.V2 RBD+SBD1 protein and an RBD+SBD1 from the original lineage was assessed by ELISA (Fig.2b). These data revealed that binding of polyclonal plasma to 501Y.V2 RBD+SBD1 was only substantially affected in a minority of cases (14 of 44 with ≥five-fold reduction, 32%). Most of the convalescent plasma/serum suffered less than four-fold reductions in total binding activity (as measured by area under the curve), suggesting a considerable non-neutralizing antibody component are still able to bind the 501Y.V2 spike antigen"
- chemeng 6y agoThis is correct, but just want to add that many may interpret this as a positive sign, it is not necessarily. In many cases, binding antibodies increase cell infectivity. Also, there is some research that indicates the presence of non-neutralizing antibodies without the corresponding neutralizing antibodies and humoral response may be a factor in the development of antibody dependent enhancement. As far as we know, it is the neutralization potency that strongly correlates with disease severity.
- NeutronStar 6y agoUnless you source something, I'm going to take this as your opinion instead.
- standardUser 6y agoIs this just one of the hundreds of variants that have been found so far but do not spread widely, or is there some reason to believe this variant is more easily spread and will become common?
- dragontamer 6y agoThis is one of the first variants that avoids our current plan of defense: antibody plasma. At a minimum, it means that treating COVDID19 may require further tests to see if we have COVID19, or... what probably will be called COVID20 or COVID21 (for 2020 or 2021, depending on when we want to pin the "origin date" of this virus variant). I'm assuming COVID20 in my ignorance... If COVID19 treatment doesn't work, doctors will then have to try COVID20 treatment. -------------- It really depends on how much COVID20 has mutated compared to COVID19, as well as how effective Pfizer, Moderna, AstraZenica, and Johnson & Johnson's vaccines are against COVID20. They've only been tested against COVID19 (the 2019 variant). We'll have to run tests to see if our defenses are good enough for COVID20, or if we have to start the vaccine race all over again.
- jupp0r 6y agoThis one is spreading more widely in South Africa and has also been found in other countries already. It has an advantage in populations that have prior immunity from natural infection.
- kube-system 6y ago> . In South Africa, genomic data highlighted that the 501Y.V2 variant rapidly displaced other lineages circulating, and preliminary studies suggest the variant is associated with a higher viral load, which may suggest potential for increased transmissibility; however, this, as well as other factors that influence transmissibility, are subject of further investigation. > As of 30 December, the 501Y.V2 variant from South Africa has been reported from four other countries to date. https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/ https://www.who.int/csr/don/31-december-2020-sars-cov2-varia...
- bjornsing 6y ago> is there some reason to believe this variant is more easily spread and will become common? Yes, there are two reasons: increasing natural immunity and vaccinations.
- Arubis 6y agoPulling directly from TFA, > Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines. Ugh; this hurts to read. The callouts there are "complete escape [from] convalescent plasma" (prior exposure won't help you), and "reduced efficacy of current spike-based vaccines" (which is all of the ones deployed, I believe).
- UncleOxidant 6y agoYeah, this is not great news. I hope the vaccine makers are looking at adding coverage for these variants to the existing vaccines. That should be relatively easy to do for the mRNA vaccines, but possibly harder for the adenovirus based vaccines like the Oxford/AZ and the J&J. The question is whether they would have to go through a full phase 3 trial for this kind of addition or would this be more like how we add coverage to different flu viruses to the annual flu vaccines?
- ashtonbaker 6y ago> That should be relatively easy to do for the mRNA vaccines That isn't super obvious to me anymore, after it was pointed out to me that the current mRNA vaccines rely on a modified sequence for the spike protein, designed to make the protein stable enough to be usable in the vaccine process (described here [1] as "antigen S-2P" - "S" for "Spike" and "2P" for the two proline substitutions in the sequence). It's my understanding that this work dates to 2017 [2], and that it might not be quick or easy to replicate for new spike protein variants. [1] https://www.nature.com/articles/s41577-020-00480-0 https://www.nature.com/articles/s41577-020-00480-0 [2] Pallesen, J. et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl Acad. Sci. USA 114, E7348–E7357 (2017).
- AndrewBissell 6y ago> The callouts there are "complete escape [from] convalescent plasma" (prior exposure won't help you) Whether prior exposure helps also depends on T-cell response. At this point it's well established that immunity lasts for some unknown period of time past when most antibodies have left the bloodstream.
- AndrewBissell 6y agoI'm curious, is this headline (which differs significantly from the one on the paper itself) making the common mistake of conflating "immunity" with "antibodies"? Just wondering if there is a difference between showing that the new strain is resistant to the antibodies as opposed to showing that it is likely to reinfect people who recovered from a previous strain.
- AndrewLiptak 6y agoWorth noting that this study isn't peer reviewed yet.
- zzleeper 6y agoWorth noting that peer review is also a bit (or a lot slow) and not perfect, and that all peer-reviewed studies have in the past been not peer reviewed.
- jgalt212 6y agoindeed. The replication crisis occurred in peer review media.
- Haunted_Cabbage 6y agoNone of which invalidates the importance of peer review. If anything, it means that more should be taking place.
- jupp0r 6y agoNote that 1. The sera they tested this against obtained antibodies through natural infection. It's not clear whether vaccine-induced immunity is protective against this variant. 2. They only tested for neutralizing antibodies, but there is still T-Cell response which could provide protection.
- wittyreference 6y agoThe primary benefit of the vaccine over 'natural' immunity (other than avoiding actual exposure) is the emphasis on neutralizing antibody formation.
- AndrewBissell 6y agoI had assumed the vaccine was also intended/believed to induce T-cell response, is that not the case? Given that they disappear within a matter of months after a natural infection, how long are the antibodies from the vaccines believed to last?
- wittyreference 6y agoOh, it is. I meant that that is also part of 'natural' immunization. The distinction between the 'natural' exposure and the vaccine is that the natural exposure targets a number of epitopes, which may or may not include effective neutralizing antibodies against the spike protein; the vaccine, on the other hand, only offers the spike as an antigen, so you know you're generating neutralizing ab.
- jupp0r 6y agoThere are vaccines in development that also target the N-protein.
- mc32 6y agoIf we can expect more surprises like this, movement will have to be curtailed till we’re sure we have things under control (like SARS). We can’t have the whole world economy in lockdown because a new strain spread because prior immunization is ineffective against the variant.
- UncleOxidant 6y agoIt would seem that the horse is already out of the barn. Flights would have needed to be curtailed much earlier. In addition, we're seeing similar mutations popping up independently in geographical areas - seems to be evolutionary pressure in these directions.
- mc32 6y agoUnderstood, but if we can contain the mutations regionally, it’s better than having them spread globally.
- UncleOxidant 6y agoThe rise of these variants shows that we have to do a much better job with genomic analysis and surveillance and we have to be willing to be more proactive about shutting down travel to/from regions where these variants show up. I'm just not sure we have the political will to do what the science would suggest - we didn't for the original covid-19 and as it spread around the world political leaders of all stripes were slow to listen to the scientists. I guess I'm not sure that's going to change.
- Loughla 6y agoI think you lost me. How can we have an unfettered economy, not limited by lockdowns AND contain mutations regionally? These two statements you have made seem to be at odds with one another. Or am I overthinking/underthinking this?
- mc32 6y agoOne affects the global economy, the alternative affects a local economy, for example.
- cs702 6y ago1. Abstract: "SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines." 2. See also: * "New coronavirus variants could cause more re-infections, require vaccine updates": https://www.sciencemag.org/news/2021/01/new-coronavirus-variants-could-cause-more-reinfections-require-updated-vaccines https://www.sciencemag.org/news/2021/01/new-coronavirus-vari... * "Can we stop a super coronavirus?": https://www.spiegel.de/international/world/can-germany-stop-the-new-supervirus-a-e9ffc207-0015-4330-8361-b306f6053e15 https://www.spiegel.de/international/world/can-germany-stop-... * Tweets by an epidemiologist at Harvard about the new variants found in Manaus, Brazil: https://twitter.com/BillHanage/status/1349943613514526723 https://twitter.com/BillHanage/status/1349943613514526723 3. A key takeaway, for me: Evolutionary paths for covid-19 that would normally be very unlikely become more and more likely as more people get infected with the virus, providing a large-scale, global playground for experimentation via random mutation. Random evolutionary events that would normally be rare become more and more likely as the numbers grow large enough.
- PeterStuer 6y agothe government of my region has decide that instead of following normal vaccination procedures, they will spread the available vaccine (Pfizer) to just give 1 dose to as many people as possible as opposed to the 2 required to be effective as per the clinical trials and the manufacturers advice. This decision is purely political, defying all biological evidence. Seems to me this is the perfect scenario to evolve vaccine resistant variants.
- bluGill 6y agoProbably not. The second dose of the vaccine is more about ensuring that you are covered for a long time. So long as everyone gets the second dose in a few months we are fine. If we wipe out COVID there is no reason to give second doses at all.
- PeterStuer 6y agoWell, I hope you are right. "Pfizer said in a statement that there are "no data" to demonstrate that a single dose of its coronavirus vaccine will provide protection from infection after 21 days." https://www.axios.com/pfizer-single-dose-data-716702dd-324f-42b9-b88d-07df43ca198a.html https://www.axios.com/pfizer-single-dose-data-716702dd-324f-...
- bluGill 6y agoWe don't know how long protection lasts after the 21 days, but we have enough data from other vaccines to make educated guesses. I wouldn't go more then a couple months.
- PeterStuer 6y agoVaccine dosage and protocol are virus specific, and this Pfizer vaccine is completely unlike other human vaccines as it is a new class (mrna).
- citilife 6y agoI for one am not concerned. The true mortality rate appears to be <1% and of that 90% are >65. What does that mean? To put it into perspective you may only know one person in your friend group which knows one person who dies. Your friends / family are more likely to die of cancer. How often do you know someone die of cancer? It's definitely unfortunate; we should all socially distance & wear N95's where possible. All of us can decide if we want to stay locked down or not. Probably half the population will, so the spread will be much lower than otherwise. The rest of the population can keep working, making money and feeding their children.
- hinkley 6y ago> How often do you know someone die of cancer? That depends on how many smokers and ex-smokers you know. It makes it all the sadder because the death was preventable. Which puts it into a similar headspace with Covid.
- pelagicAustral 6y agoBecause obviously only smokers die of cancer...
- hinkley 6y agoI can always count on developers to ignore the emotional cost of a decision or action and only count the wall clock time. It's why Scrum is fundamentally rotten at its core.
- lostapathy 6y agoDeath rate will surely go up if there are multiple strains of this going around that are different enough you could catch 'em all, over time.
- kube-system 6y agoIt is important to note that the current mortality rate is the mortality rate with treatment, and with varying degrees of spread mitigation measures. If hospitalization rates exceed the available beds, the mortality rate will rise.
- beamatronic 6y agoStrange, it’s almost like you should do everything humanly possible to avoid getting this.
- godmode2019 6y agoQuestion: How would this affect severity? My basic understanding is because this is a new virus humans have very little existing immunity, which is the problem and why we don't die from colds. Over time our bodies get better at dealing with the virus and the virus gets better dealing with us. I read a paper on hn to this effect a little while ago, I'll provide source if needed.
- CyberRabbi 6y agoI think in general not causing death in the target host is a naturally selected trait in viruses. The least lethal viruses are the ones that spread the most. This has been observed in herpes, which has evolved to infect nervous system cells but explicitly not nerve cells in the brain (which would cause death). So considering that, perhaps future strains of COVID will reduce their lethality while increasing their ability to infect.
- bluGill 6y agomaybe. Measles was around for years and deadly. It (much like covid) could spread before it killed. Also like COVID it doesn't kill everyone it infects. HIV/AIDS mutates a lot, but doesn't seem to be mutating in such a way as to not kill the host, you can be infected for 5-10 years before it kills you which is plenty of time to pass it on. It appears that a tiny number of people have a genetic immunity to HIV/AIDS, and so they could be the only survivors - which would mean that left unchecked humans will mutate to not be vulnerable to AIDS. (modern medical treatment has made significant progress on HIV/AIDS that I'm ignoring for this point)
- CyberRabbi 6y agoInteresting... the common cold and the flu also tend to mutate to be resistant to past immunity. I wonder if we’re on a the cusp of finally finding cures for these types of rapidly mutating viruses.
- beamatronic 6y agoOr you could just wear a mask and social distance and not congregate indoors with random strangers for long periods of time
- kirykl 6y agoeternal 2020
- binaryblitz 6y agoFor your entire life? IDK about you but I'm ok with getting a common cold or the flu once every few years to live a normal life.
- mikeymz 6y agoEvery few years? My experience is more like every 6 weeks in the winter. Even with lock down I have caught the second cold of the season. I am guessing you don't have kids
- NeutronStar 6y agoSo you go and get vaccinated, don't force everyone to wear a mask forever and live in perpetual lockdown.
- dougmwne 6y agoThese are necessarily temporary measures. Life cannot go on forever with these restrictions in place. Either medical science will find a way to limit the danger or people will adapt to their new, more dangerous world. I am not an anti-masker, but asking for permanent social distancing is not realistic.
- wk_end 6y agoThe current headline (“strongly resistant to past immunity”) is editorialized and not what the research here shows. It’s resistant to donor antibodies, which is definitely unfortunate and concerning, but there’s more to immunity than just antibodies, and even more to antibodies than just the ones donated. Preliminary research [1] shows that vaccines are still effective, at least, and likely that implies natural immunity is still effective too. [1] https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1 https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1
- gewa 6y agoI agree, the headline is definetly not what the research shows. See my other comment on non-neutralizing antibodies. Please change the title to the original one.
- mikem170 6y agoYep. It's an irresponsible headline, like so many others, renewing panic even amongst the crowd here. I hope your comment and others like it are not lost amongst all the others so quick to call for a doubling-down of imposed quarantines and lock downs without regard for collateral damage, based on their partial knowledge of the immune system and lack of perspective.
- hansdieter1337 6y agoThe paper you cited actually states that existing vaccines are less effective: “However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations.”
- gewa 6y agoPlease note, that neutralization by antibodies is only one of the many possible ways how our immune system can take action. Antibody recognition is still possible with the found mutant: "To determine whether 501Y.V2 is still recognized by non-neutralizing antibodies, the binding of polyclonal sera (from Fig.2a) to a recombinant 501Y.V2 RBD+SBD1 protein and an RBD+SBD1 from the original lineage was assessed by ELISA (Fig.2b). These data revealed that binding of polyclonal plasma to 501Y.V2 RBD+SBD1 was only substantially affected in a minority of cases (14 of 44 with ≥five-fold reduction, 32%). Most of the convalescent plasma/serum suffered less than four-fold reductions in total binding activity (as measured by area under the curve), suggesting a considerable non-neutralizing antibody component are still able to bind the 501Y.V2 spike antigen" Its also worth to note that only 44 plasma samples were used from individuals out of a population where the virus probably originated.
- chemeng 6y agoLooks like this was posted again, so I'll post my response here as well: This is correct, but just want to add that many may interpret this as a positive sign, it is not necessarily. In many cases, binding antibodies increase cell infectivity. Also, there is some research that indicates the presence of non-neutralizing antibodies without the corresponding neutralizing antibodies and humoral response may be a factor in the development of antibody dependent enhancement. As far as we know, it is the neutralization potency that strongly correlates with disease severity.
- timr 6y agoEverything you've written is speculation or assertion, whereas the OP's comment is a factual statement about the limitation of the work. They're showing that this mutation escapes a few particular antibodies. That's all. At the very least, the current headline "strongly resistant to past immunity" is editorialized and completely misleading, and should be changed to the title of the paper. > In many cases, binding antibodies increase cell infectivity. Citation absolutely required. I am unaware of an example of this, let alone "many cases".
- 6y ago
- CWuestefeld 6y agoThis is how the FDA's refusal to balance up-side risk is going to damage all of us. They're only interested in minimizing the risk from a treatment itself, and pay little to no attention to the risk from not having any treatment. It's been a full year since the first vaccines were formulated, and it took the FDA 11 months to give the OK. That was a large streamlining of their normal processes, but not a meaningful balancing of risk, the standards remained the same. In the meantime, the virus has had millions of opportunities to mutate like this. If we'd accepted a bit more risk, we could have significantly decreased its opportunities to mutate. At least in this case, the virus can't mutate faster than our ability to formulate a new vaccine. Whether we can retool vaccine manufacturing I don't know. But so long as the FDA won't allow us to react quickly, the hole we're in keeps getting deeper.
- nicpottier 6y agoThis is an interesting take for sure that I hadn't heard before. Do you have more information on how they could have accelerated things? If feels like the risk of shipping a vaccine that later is found to have adverse side effects would be so dangerous to the trust of the FDA that it would be really dangerous. Think of the shattered trust on both the FDA side and on vaccines in general, feels like maybe that would be too big a risk to take.
- kube-system 6y agoThe FDA is slow? Compared to what? They approved the first vaccine 3 days after the NHS. If your window of success vs. failure is very small, you simply have to test before you push to prod. Especially when using a technique with a long history of failed attempts.
- valarauko 6y agoOn the flip side, you have a sizable portion of the population that feels even the Emergency Use Authorization (EUA) by the FDA was rushed (To be clear, I'm playing the Devil's Advocate here - I personally don't disagree with the FDA's decisions, and got my own shot weeks ago) Genuine Q: which steps of the process do you see as superfluous? Pfizer announced the end of the phase 3 trials on November 18th, they submitted an application to the FDA for EUA on the 20th of November (or sometime shortly after), and the EUA was granted on the 11th of December. It didn't take 11 months for the FDA to give the OK. It took 11 months to design a vaccine from scratch, conduct phase I safety trials, phase 2 human safety and dosage trials, and a phase 3 trial to determine efficacy. This includes actual production of the mRNA & its vector in quantities sufficient for the trial, subject recruitment, shipping logistics worldwide to participants, administration of the test doses, data collection, analyses, and compiling results. Honestly, 11 months from start to finish seems like an amazingly short time to achieve so much.
- rimliu 6y agoAnd then there is this: https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1 https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1
- dkural 6y agoToday Biontech also announced results showing induces a similarly strong immune response against the new variants, although I haven't read the details. .
- deleted 6y ago[deleted]
- knowaveragejoe 6y agoLink? Edit: If you're talking about this press release, I believe this is referencing a different variant. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-puresults-study-showing-covid-19 https://www.pfizer.com/news/press-release/press-release-deta...
- rflrob 6y agoIt is a different variant, but both the 501Y.V2 ("South African lineage" tested in OP) and B.1.1.7 ("UK lineage" tested in the Pfizer study you linked) have the N501Y spike mutation, which (I gather) is the residue of particular concern.
- LatteLazy 6y agoInteresting to see what this will mean for the vaccines currently in use. If they generate the spike protein and the spike protein is significantly altered in the new variant, we in the uk are fucked.
- dang 6y agoThe submitted title ("New mutation of COVID19 strongly resistant to past immunity") broke the site guidelines by editorializing, and probably also by being misleading. Please don't do that. If you want to contribute your interpretation, that's fine, but do so in a comment—then your interpretation is on a level playing field with everyone else's. On HN, being the user to submit an article doesn't come with any special rights about how to frame it for others. "Please use the original title, unless it is misleading or linkbait; don't editorialize." https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
- mazsa 6y ago"expert reaction to preprint reporting that the South African SARS-CoV-2 variant 501Y.V2 escapes neutralisation by COVID-19 donor plasma" https://www.sciencemediacentre.org/expert-reaction-to-preprint-reporting-that-the-south-african-sars-cov-2-variant-501y-v2-escapes-neutralisation-by-covid-19-donor-plasma/ https://www.sciencemediacentre.org/expert-reaction-to-prepri...