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AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction
- aphextron 6y agoIt's important to note that the AstraZeneca vaccine is adenovirus based [0], not mRNA based like the Pfizer and Moderna candidates. It was to be expected that this approach could cause more complications. mRNA vaccines have their own issues, but they do not involve live viruses being injected [1]. Instead they use lipid nanoparticles as a substrate to enter the body's cells [2]. [0] https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-and-oxford-university-announce-landmark-agreement-for-covid-19-vaccine.html https://www.astrazeneca.com/media-centre/press-releases/2020... [1] https://www.phgfoundation.org/briefing/rna-vaccines https://www.phgfoundation.org/briefing/rna-vaccines [2] https://www.nature.com/articles/s41586-020-2639-4 https://www.nature.com/articles/s41586-020-2639-4
- mrfusion 6y agoSo how does this one work? Live adeno’s?
- aphextron 6y ago>So how does this one work? Live adeno’s? Yes. It uses a live (weakened) chimpanzee adenovirus to insert the spike protein. https://www.drugs.com/history/azd1222.html https://www.drugs.com/history/azd1222.html
- mrfusion 6y agoDo the adenos actually have to infect the cells to produce the spikes?
- dogma1138 6y agoYes, they don’t replicate virons that could be assembled the virus was modified to mainly replicate the spike proteins since your cells send samples of anything they replicate to the cell wall for your immune system to monitor and sample this is how the adaptive immune response is achieved.
- kurthr 6y agoExactly, for strong long term response you want T-cell involvement.
- im3w1l 6y ago> cells send samples of anything they replicate to the cell wall for your immune system to monitor Wow nature is truly a marvel! How do they do that? Or where could I read more?
- deleted 6y ago[deleted]
- nextos 6y ago> Wow nature is truly a marvel! How do they do that? Or where could I read more? Read about the HLA/MHC class I pathway. And also about JAK/STAT1, which is how cells decide if they are infected.
- ethbr0 6y agoThe chimpanzee adenovirus is used as a vector, with its payload replaced with instructions to manufacture SARS-CoV-2 spike protein. Virus enters body, hopefully survives immune system long enough to insert instructions into your cells, your cells churn out tons of copies of coronavirus spike protein, your immune system sees the surfeit of spike protein and develops a response (antibodies and T* cells). https://blogs.sciencemag.org/pipeline/archives/2020/04/23/a-close-look-at-the-frontrunning-coronavirus-vaccines-as-of-april-23 https://blogs.sciencemag.org/pipeline/archives/2020/04/23/a-...
- karmicthreat 6y agoThought Emporium has a decent video where he modifies an Adenovirus to inject the lactase gene into the cells of his intestinal tract. https://www.youtube.com/watch?v=J3FcbFqSoQY https://www.youtube.com/watch?v=J3FcbFqSoQY
- kevin_b_er 6y agoIt could still be an immune system misfire. A vaccine is trying to create an large immune system response enough that the real infection is thwarted. With that, a misfire can happen with any vaccine attempt, because an immune response is what's required.
- EForEndeavour 6y ago> rather than producing them outside the body and then injecting them That's not what the Oxford/AZ vaccine does, is it? From what I understand, it's a viral vector vaccine engineered to deliver DNA that encodes the SARS-CoV-2 spike protein into human cells and induce them to express the protein, stimulating the immune response. The plan was never to introduce spike protein "produced outside the body." The mechanism of action is getting the body to produce spike protein and learn to attack it as foreign. If the Oxford/AZ vaccine doesn't "take advantage of your own cells to produce the spike protein," I don't know what does. https://labblog.uofmhealth.org/rounds/top-5-covid-19-vaccine-candidates-explained https://labblog.uofmhealth.org/rounds/top-5-covid-19-vaccine...
- sudosysgen 6y agoYes, that was made in comparison to conventional vaccines that either use inactivated viruses or viral proteins
- dogma1138 6y agoPlenty of vaccines both today and historically used LAV or other natural strains of the virus when possible.
- kurthr 6y agoYes, the ChAdOx is an adenovirus carrier (chimp? to minimize human pre-infection) while Moderna and BioNTech as the parent states involve injection of mRNA (not DNA although there are other vaccines that do that) lipid particles that human cells then generate spike protein to simulate viral infection. There are still other attenuated virus and other vaccines under development, they just haven't reached Phase III. Novavax even does something similar to what you describe (spike proteins with adjuvant), but it's also not past Phase I/II.
- axaxs 6y agoI think COVID is going to be make or break for mRNA, at least for infectious disease. It's either going to usher in an exciting new era of treatments, or we're going to see a lot of funding dry up and shops close. I for one obviously hope for the former, but given the prior actions/statements of some in Inovio, Moderna, et al, it gives me pause.
- raxxorrax 6y agoYou cannot roll out such a vaccine on a large scale within a at least a year. Far too many unknowns compared to the virus itself.
- yread 6y agoWhere it says "serious adverse reaction" do they mean the adverse reaction was serious or that it's an actual grade 3 adverse event (SAE)? https://en.wikipedia.org/wiki/Serious_adverse_event https://en.wikipedia.org/wiki/Serious_adverse_event
- SparkyMcUnicorn 6y agoThe article seems to indicate that this could be a SAE, but also that "the participant is expected to recover".
- _jahh 6y agosurviving with quadriplegia would be recovery but I believe an SAE
- emmanueloga_ 6y agohow do they find volunteers for such a trial? If I get it right, the risks are high (including death?) so seems like a big risk, and I suppose they need to start with someone that's healthy to avoid confounding factors?
- jedberg 6y agoThe risk of getting the virus is death too. If you're already in a risky position (say you're a teacher in a district that is insisting on in school teaching or a paramedic or cashier at a grocery store) then the vaccine trial might be the less risky option.
- dan_quixote 6y agoThat's a terrific invitation for bias.
- djsumdog 6y agoUnless you're a teacher over the age of 55, your risk, even around a bunch of school children, is incredibly low (95% of fatalities in the US are over 55, with most of those being over 65). I've read a few of these "long term damage" studies that are scaring everyone. Of the 60+ people in the UK one published by the journal in Charlottesville, most of them were elderly or in "high risk" jobs (it didn't mention what jobs for privacy. Health care workers? grocery store? who knows).
- notatoad 6y agomaybe this is off-topic, but it's interesting to me that this is the first time i've heard this referred to as the "astrazeneca vaccine". all the previous good-news stories seemed to call it the oxford vaccine.
- dekhn 6y agoThis is a US trial, AZ is listed as the Sponsor for the trial, https://clinicaltrials.gov/ct2/show/NCT04516746 https://clinicaltrials.gov/ct2/show/NCT04516746 and the PIs listed are both at US.
- seedless-sensat 6y agoExcept the adverse reaction was not in the US trial.
- dekhn 6y agoI followed the first link in the stat article, which says "A large, Phase 3 study testing a Covid-19 vaccine being developed by AstraZeneca and the University of Oxford at dozens of sites across the U.S. has been put on hold due to a suspected serious adverse reaction in a participant in the United Kingdom" As I read that, it was a UK participant in a AZ and US-run study.
- BickNowstrom 6y agoAstraZeneca and Oxford have subjects in the US, UK, Brazil, and South-Africa. The aim was to have diverse make-up of the testing groups, to have an order of magnitude more people in the Phase 3 trial than normal for a vaccine, to test in countries with high infection rates, and to deliver the results on 15th of September. A British subject from the British trial got ill. I presume these countries have deals with Oxford/AstraZeneca so if a safe vaccine is available, they get guaranteed access. I've heard India is already producing the vaccine ahead of the Phase 3 conclusion. The phase 3 is only on hold since it is not clear if the vaccine was the cause. There are other causes for the adverse reaction, such as viral herpes infection, or onset nerve diseases not caught during subject checkup. Since not all vaccines offer 100% protection (while still being useful), COVID may have also been the cause of spinal nerve inflammation.
- hartator 6y agoIs this one of the two favorites?
- Marazan 6y agoYes. The one in pole position. Until now.
- mrfusion 6y agoIs that why the market was down today?
- marc__1 6y agoNo, the AZN announcement was made after the market closed. Take for instance Moderna, who was -13% today, and is +3.7% after-hours
- codeisawesome 6y agoNot tracking the real world anymore
- zerobits 6y agoThe Moderna mRNA vaccine was producing 103 degree fevers (and passing out) in a Phase 1 volunteer. [1] If that's the reaction in small sample with a healthy 29 year old (most volunteers had high fevers), I can't imagine old or unhealthy people will be unharmed. I was more concerned about the mRNA vaccines being at risk initially. Things aren't looking great... [1] https://www.statnews.com/2020/05/26/moderna-vaccine-candidate-trial-participant-severe-reaction/ https://www.statnews.com/2020/05/26/moderna-vaccine-candidat...
- pageandrew 6y agoPhase 1 trials are used to determine dosage. Different participants are given different doses of the vaccine so researchers can identify the proper dosage with maximal efficacy and minimal side effects. The 29 year volunteer who experienced the 103° fever received the highest dose of the vaccine given out during the Phase 1 trial. Such a adverse reaction is not unexpected during a Phase 1 trial, but the vaccine did move forward to Phase 2 and Phase 3 so it appears that the lower dosages do not trigger such a reaction.
- roody15 6y ago“The platform has not been used in an approved vaccine, but has been tested in experimental vaccines against other viruses, including the Ebola virus.” hmmm... this method of vaccination has never been used in an approved vaccine.
- alkonaut 6y agoYou’ll find that’s the case for several of the front runners.
- manicdee 6y agoAll medicines were new at some point in time. Your anti-vax fear mongering doesn't belong here.
- pieceofcakedude 6y agoLOL! Pointing out that an unfamiliar vaccine technology has never been used before is now officially anti-vax fear mongering.
- puranjay 6y agoI swear the pro vaxxers are as much of a cult now as the anti vaxxers. I've been attacked so many times for simply saying that I would wait a while for results before trusting a rushed vaccine, especially one that has a massive financial upside for the creator.
- manicdee 6y agoI mean you could check the other comments under that one to see that it's a deliberate trigger for anti-vax fearmongering. It's one thing to be skeptical, it's another to be a denier. If you can't pick up on the cues then you'll never be able to fight misinformation.
- toast0 6y agoPlenty of medicines were new and then removed from the market. Being cautious about new techniques seems reasonable, given the history of medicine. (And frankly, a lot of other fields) It would be nice to be able to say this new vaccine is based on existing methods that we know from years of experience are very safe; but we can't for this candidate. That doesn't make it less safe (or more safe), but it makes the risk more unknown.
- volkse 6y agoThe russian vaccine is also based on adenovirus vectors. Not clear if the method of delivery is to be blamed here, but it could be the cause for the adverse effects..
- YarickR2 6y agoThey (russians) are conducting large scale phase 3 experiment, with up to 40k volunteers. Need to watch closely; most of the volunteers are in Moscow, and it will be difficult to conceal high rate of side effects .
- kurthr 6y agoCareful, because a "high rate" would be ~1/100k. Even a two SAEs in that cohort size, would be a huge deal and enough to shut down most efforts. Edit: also note that the Russian Gamaleya vaccine is actually 2 vaccines one with a human adeno virus carrier and the other with a (chimp?) Ad5 and Ad26. So you could have a response to either one of them, or both. The problem with using a human viral carrier is that pre-exposed might fight it off without developing nCoV immunity.
- tinus_hn 6y agoPretty dumb because the damage from the real virus, both the damage from the illness and from the measures against it, is much worse than that.
- ck2 6y agocan't find the link at the moment but there is now some academic comment that the russian data has some fakeness to it
- dang 6y agoOther ongoing Covid vaccine thread: https://news.ycombinator.com/item?id=24411540 https://news.ycombinator.com/item?id=24411540
- fancyfredbot 6y agoNot good news, but don't panic - as the article says "Clinical holds are not uncommon", and “in large trials illnesses will happen by chance but must be independently reviewed to check this carefully.”
- klmadfejno 6y agoI agree, don't panic. However that phrase isn't especially useful. Clinical trials failing isn't uncommon either.
- dvirsky 6y agoOne bit of positive impact this might have is to increase people's confidence in the safety of the process.
- ummonk 6y agoYeah given the size of their trial there's a good chance this is a reaction to something else rather than the vaccine.
- redisman 6y agoThere are also multiple other vaccines using completely different techniques to trigger immunity in stage 3 trials if this ultimately fails
- zobzu 6y agoI wonder what are informed positions about these vaccines potentially modifying and patenting your DNA or using aerogels (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539078/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539078/) since these stories float around in particular for this vaccine to my understanding. Are these all bs? What's the risk?
- zamalek 6y ago> modifying and patenting your DNA In order to do what, exactly? These bizarre conspiracy theories always lack a specific goal by the supposed perpetrators. > using aerogels So, what if they did?
- mandelbrotwurst 6y agoYou're lacking in imagination if you can't come up with ways that someone might be able to profit from legal rights to or the ability to modify the genetic code of other persons.
- refurb 6y agoBut nobody's DNA is being modified with these vaccines.
- djsumdog 6y agoI'm having trouble more details information on how the messenger-RNA based vaccines work. They appear to transcribe proteins in the cytoplasm. I think the fear is that these vaccines may contain some combination of Reverse Transcriptase and Integrase enzymes. Do they contain these enzymes? If not, do they simply try to get your cells to create spike proteins?
- DrAwdeOccarim 6y agoThey do not contain reverse transcriptases or integrases. Just wondering why you think they would?
- 6y ago
- tus88 6y agoSomeone better come up with one. I don't want another year of this bull.
- djsumdog 6y agoIt's unlikely. I'm much more likely fatalities will drop to zero per week before the end of the year in countries with high spread and we'll have herd immunity (which is where Sweden is at now).
- 0x1A567BBF 6y agoSweden is nowhere close to achieving herd immunity (as everyone knows).
- logicchains 6y agoThen home come their case rate just keeps falling? And their death rate. And unlike the countries that locked down, they're not experiencing a second wave of cases.
- tasogare 6y agoEven in countries where a second wave is happening, it’s a wave of infection only, not deaths. There is not reason to be scared of a disease that don’t kill. International travel restrictions should be lifted. We don’t need to wait for a vaccine that might be more a dangerous than to virus it’s supposed to fight. Current practices in East-Asia have shown to be enough to handle the thing.
- kuhewa 6y agoThere is not reason to be scared of a disease that don’t kill. What about one that causes permanent lung and/or heart damage?
- 6y ago
- jameson 6y ago> It was not immediately clear who placed the hold on the trial, though it is possible it was placed voluntarily by AstraZeneca and not ordered by any regulatory agency. The nature of the adverse reaction and when it happened were also not immediately known, though the participant is expected to recover, according to an individual familiar with the matter. What would be a reason why they don't disclose this detail immediately but only to tell public the trial is on hold?
- lowwave 6y agoIt is big pharm. What else do you expect? A little research you will find no big pharm can be trusted.
- lowwave 6y agoWhat is meant by that is vaccine and all FDA type of drug should not be trusted unless they have several decade if not intergeneration studies to back it up.
- TheSpiceIsLife 6y agoThis is a medical treatment sort of scenario, trial participant confidentiality regulations probably prevent release of anything specific about the case.
- tptacek 6y agoWhat would be the reason to disclose the details publicly? You can't do anything with the information right now; the vaccine isn't available to you.
- roland00 6y agoThe illusion of control. It is the same reason people doomscroll on twitter hoping more information will somehow how change the result. Our brains, all human brains, are not rational but instead are their own thing.
- 6y ago
- reese_john 6y agoAccording to the NY times, the adverse reaction was transverse myelitis > The individual also said that a volunteer in the U.K. trial had been found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. More at: https://www.nytimes.com/2020/09/08/world/covid-19-coronavirus.html?smtyp=cur&smid=tw-nytimes https://www.nytimes.com/2020/09/08/world/covid-19-coronaviru...
- joshgel 6y agoTransverse myelitis, usually causes by viral infections, can cause complete paralysis below the level of the lesion. Just like a transection of the spinal cord. Quite serious, I would guess determining the etiology in this case is going to be critical, but very hard to do. Can also be autoimmune, perhaps triggered by vaccine. Or, in this case, could be triggered by the adenoviral vector used in the vaccine.
- tdrp 6y agoSo if this was triggered by the vaccine (rather than the adenoviral vector), would it mean that this person might have also had TM if they had caught Covid19?
- est31 6y agoThat's what you have studies for! Glad they caught it before it got into the wild. Also, it's really great that there are multiple vaccines. Just imagine what happens when everyone gets a single vaccine that turns out to very often cause an adverse reaction...
- LeoNatan25 6y agoAnd this is why trials must be allowed to run their course, not use vaccines as political propaganda, like what the Russian gangster and the orange clown are doing for their own political gains.
- WalterBright 6y agoAll drugs have adverse side effects. The idea is the "therapeutic index" being the ratio of the good to the bad. In this case, balancing the risk of the vaccine against the reality of all the deaths that covid is causing. Waiting for a zero risk vaccine is not the optimal decision.
- tjmc 6y agoQuestion for people who understand the Phase 3 process - would the first step in an investigation of this type be to "unblind" the patient with the adverse reaction to see if they got the vaccine or a placebo? Seems to me if the reaction wasn't caused by the vaccine there's a 50/50 chance this person received a placebo. In which case, you could instantly discount the vaccine being the cause.
- abiogenesis 6y agoInterestingly placebo-induced adverse reaction is also a thing: https://pubmed.ncbi.nlm.nih.gov/10367099/ https://pubmed.ncbi.nlm.nih.gov/10367099/
- lbeltrame 6y agoThe principal investigator of the trial knows who got placebo and who did not, although neither the people working on the data nor the clinical staff know. It's likely that the participant will be "unmasked" to see why the adverse event occurred.
- deleted 6y ago[deleted]
- ageitgey 6y agoI'm in the trial. We all got little cards with our trial number to keep in our wallet. If we get seriously ill or end up in a hospital, there's a number for the doctor to call to unblind us if necessary. So there is definitely a procedure in place. Even if the person got the vaccine, the illness could be unrelated. They need time to investigate and this is the proper procedure to follow. This happened once before earlier in the trial, but it wasn't reported as widely and there want a media frenzy. There is nothing wrong with the media reporting this, but it would be great if the media was better at contextualizing information instead of maximizing clicks with scary headlines.
- yalogin 6y agoThis is the vaccine trump set his hopes on to be available by November. Isn’t it?
- hestefisk 6y agoOne of them. It’s funded through Operation (OS/2) Warp Speed.
- aaron695 6y agoWhat's really funny is even if they can prove it's not an adverse reaction the anti-vaxers will run with this forever. If you can prove anything. If it's not real. And absolutely this is just the beginning. These things normally don't make the news. This will be all the time over the hundreds of vaccines and when they get rolled out properly there will be hundreds of stories to pick from.