Moderna’s SARS-CoV-2 Vaccine Phase I Data(blogs.sciencemag.org)
blogs.sciencemag.org
Moderna’s SARS-CoV-2 Vaccine Phase I Data
https://blogs.sciencemag.org/pipeline/archives/2020/07/15/modernas-phase-i-data
174 comments
What's the issue with the safety profile?
Probably referring to the fact the majority had fairly noticeable side effects especially with the second dose.
One person taking the highest dose had a 103+ fever with the second...
If this is happening in healthy young people, what will the side effects look like for older or more vulnerable people who actually need it the most?
One person taking the highest dose had a 103+ fever with the second...
If this is happening in healthy young people, what will the side effects look like for older or more vulnerable people who actually need it the most?
They already eliminated the highest dose given the lower dose also produced significant antibodies.
yeah, and I don't see fever as a significant negative symptom. It's really just an indication that the immune system is working.
Fever is very common in vaccines, especially in children.
Fever is very common in vaccines, especially in children.
It may not be significant to you, but to an epidemiologist this means a certain fraction of the overall population is going to die.
As others have mentioned, the highest dose did have some adverse events, and has been withdrawn from consideration. Here's his own words on twitter.
https://twitter.com/ichaydon/status/1265275383798050819
https://twitter.com/ichaydon/status/1265275383798050819
> If this is happening in healthy young people, what will the side effects look like for older or more vulnerable people who actually need it the most?
May be better on that axis (only way to know is to do the trial). Efficacy, on the other hand, is likely to be lower. Both sides of the same coin: you probably get less of a response from the old.
May be better on that axis (only way to know is to do the trial). Efficacy, on the other hand, is likely to be lower. Both sides of the same coin: you probably get less of a response from the old.
Test subjects were 18-55 — I guess I wouldn't say that's exclusively "healthy young people" other than in comparison to the 80+ group which is most in danger. But we are mostly on the same page — is the cure worse (or equally bad) as the disease for the 60-70, 70-80, 80+ populations?
Even if the vaccine is not suitable for the older groups, high vaccination rates in younger people may be enough to drop the rate of infection significantly below 1.0, eventually conferring herd immunity for the immunocompromised.
Even if the vaccine is not suitable for the older groups, high vaccination rates in younger people may be enough to drop the rate of infection significantly below 1.0, eventually conferring herd immunity for the immunocompromised.
The <45years of age US population in 2010 accounted for 60% of the total. Depending on what the threshold for herd immunity actually is, it could be "enough" to have everybody outside risk groups vaccinated. Even if we don't achieve herd immunity then, it does put us closer to it, meaning fewer people in the risk population would die.
https://www.census.gov/prod/cen2010/briefs/c2010br-03.pdf
https://www.census.gov/prod/cen2010/briefs/c2010br-03.pdf
> Probably referring to the fact the majority had fairly noticeable side effects especially with the second dose.
Did anyone look at the actual data? [1, Table S1-S3]
At the 100 μg 2nd dose, the most frequent moderate symptoms were fatigue (40%, "some interference with activity"), chills (26.7%, "some interference with activity"), and headache (26.7%, "repeated use of non-narcotic pain reliever > 24 hours or some interference with activity"), with no severe events reported.
In other words, pretty much what you'd expect if you asked your immune system to floor it. I wouldn't characterize these as concerning.
In all probability, we won't see sufficiently numerous cohorts until Phase II is published, Phase III is in process. Remember, this was n=15 for most arms.
> One person taking the highest dose had a 103+ fever with the second...
That's why they standardized on the 100 μg dose for Phase III [2], as a result of Phase I/II safety profile and efficacy.
[1] https://www.nejm.org/doi/suppl/10.1056/NEJMoa2022483/suppl_f...
[2] https://investors.modernatx.com/news-releases/news-release-d...
Did anyone look at the actual data? [1, Table S1-S3]
At the 100 μg 2nd dose, the most frequent moderate symptoms were fatigue (40%, "some interference with activity"), chills (26.7%, "some interference with activity"), and headache (26.7%, "repeated use of non-narcotic pain reliever > 24 hours or some interference with activity"), with no severe events reported.
In other words, pretty much what you'd expect if you asked your immune system to floor it. I wouldn't characterize these as concerning.
In all probability, we won't see sufficiently numerous cohorts until Phase II is published, Phase III is in process. Remember, this was n=15 for most arms.
> One person taking the highest dose had a 103+ fever with the second...
That's why they standardized on the 100 μg dose for Phase III [2], as a result of Phase I/II safety profile and efficacy.
[1] https://www.nejm.org/doi/suppl/10.1056/NEJMoa2022483/suppl_f...
[2] https://investors.modernatx.com/news-releases/news-release-d...
Here is an article going over the person with the adverse reaction [1]. Its a pretty scary read as the patient was 29 and seemed healthy. Like others have said this dose will not be used going forward. And these phase 1 trials are meant to find cases like that so the correct dose can be found.
[1] - https://www.statnews.com/2020/05/26/moderna-vaccine-candidat...
[1] - https://www.statnews.com/2020/05/26/moderna-vaccine-candidat...
INO-4800 phase I peer review results will be out soon.
> Very low CD8 T-cell responses
Do we know if this is actually an issue? A lower CD8 t-cell response might be expected given it's an RNA vaccine.
Do we know if this is actually an issue? A lower CD8 t-cell response might be expected given it's an RNA vaccine.
Which vaccines are more promising in terms of longer term immunity? Bloomberg reports CanSino one seems to be better than Moderna on that and it only requires one shot.
Phase 1 studies don't test the efficacy of the drug, just what kind of side effects are observed. Phase 2/3 is where the drug is tested to see if it actually works.
Not just side effects in this case.
People are skeptical about CanSino due to the way it works and, right or wrong, worries about Chinese data.
The Oxford vaccine is the front runner. They're doing several Phase III trials right now, and people are taking that to be a good sign - that they want to present plenty of evidence of efficacy.
The downside is that it's two doses and you're still going to get COVID-19. It's just that the effects are far less severe.
The Oxford vaccine is the front runner. They're doing several Phase III trials right now, and people are taking that to be a good sign - that they want to present plenty of evidence of efficacy.
The downside is that it's two doses and you're still going to get COVID-19. It's just that the effects are far less severe.
Well, these are still the "will it kill a human" rounds of testing, so any predictions are premature. As are confident guesses and gut feelings.
I think we're at about "vague hunch" certainty on how well these vaccines will work in the field.
I think we're at about "vague hunch" certainty on how well these vaccines will work in the field.
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> smells of propaganda
That breaks the site guidelines, and we ban accounts that do that, so please don't. Your comment would be just fine with the link and the second sentence.
https://news.ycombinator.com/newsguidelines.html
That breaks the site guidelines, and we ban accounts that do that, so please don't. Your comment would be just fine with the link and the second sentence.
https://news.ycombinator.com/newsguidelines.html
It’s possible that longer term immunity (> 3 months) isn’t even possible. There’s initial evidence of reinfections in that time frame, which means that vaccines would only last about that long and “herd immunity” is impossible:
https://www.vox.com/2020/7/12/21321653/getting-covid-19-twic...
https://www.vox.com/2020/7/12/21321653/getting-covid-19-twic...
I asked a family member(who worked in pharma) the same thing, he said if that is the case you still don't need to worry, basically its booster shots 2-3 times a year until its gone throughout the population. What is slightly worrying is what about less advanced countries who can't get this many doses.
So do we solve that with 4x a year vaccination?
At least until something better comes along.
Wouldn't it be sufficient to just keep it up until you reach a point where you've had a couple weeks with no known active cases in your country? (Assuming similar for the rest of the world, with travel restrictions or quarantines on people traveling from places where there are active cases).
In places with good contact tracing, they should mostly be able to keep it at near zero after that point by tracing and self-quarantine, occasionally needing to use the vaccine on a whole city if you find that you had a super-spreader event.
In places without good contract tracing, it would be similar except the threshold at which you need to vaccinate the city would be lower.
In places with good contact tracing, they should mostly be able to keep it at near zero after that point by tracing and self-quarantine, occasionally needing to use the vaccine on a whole city if you find that you had a super-spreader event.
In places without good contract tracing, it would be similar except the threshold at which you need to vaccinate the city would be lower.
> up until you reach a point where you've had a couple weeks with no known active cases in your country?
This point never came for influenza anywhere, why would you think it will come for COVID19, a much more contagious and invisible in many more cases virus?
This point never came for influenza anywhere, why would you think it will come for COVID19, a much more contagious and invisible in many more cases virus?
Is that the same influenza that keeps spreading year over year? Can you please explain how does the virus stay viable over long periods of time without spreading from host to host?
I would very much like a real explanation for this question from some expert in virology. But I just assume in some kind of similar way to how measles came back in Canada among the antivax community in recent years.
They are anti-vaxxers, yes, so no wonder that they could technically get measles, but where did it come from? It was completely irradicated because most people had the immunity. The virus should have died off and disappeared from the face of the planet. And yet here were are. There must mechanisms for viruses to survive this.
They are anti-vaxxers, yes, so no wonder that they could technically get measles, but where did it come from? It was completely irradicated because most people had the immunity. The virus should have died off and disappeared from the face of the planet. And yet here were are. There must mechanisms for viruses to survive this.
30% of USA and especially Trump voters won't take the vaccine.
Is the antivaxxer movement really at 30%?!
well the president of the USA is an anti-vaxxer...
That’s assuming that everyone in your city is vaccinated, and that the vaccine is 100% effective.
We’ve had a measles vaccine for three generations, we still have the measles.
We’ve had a polio vaccine for three generations, polio is not eliminated.
We’ve had a measles vaccine for three generations, we still have the measles.
We’ve had a polio vaccine for three generations, polio is not eliminated.
i'm very pro-vaccine in general (grew up in USSR and, until coming to US, didn't know that "anti-vaccine" can even exist in modern society :), yet recently and very surprisingly for myself i caught myself thinking that i will be very hesitant about getting a vaccine which is rushed through Trump's FDA to meet election day targeting schedule and to get the first dibs on the Operation Warp Speed billions - i think Trump's second term is a direct function of whether he'd triumphantly announce vaccine in the last week of October or not, and i fully expect that he would. Choosing between such a vaccine and a straight coronavirus with well-known low risk profile for my group - i'm still undecided :) So, i'd guess there would be a lot of people who wouldn't be rushing to get the vaccine.
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If you're still a citizen of Russia, I believe you could get Russian vaccine instead, they are making a good progress too
i'd say that is a great "English humor" level joke, and i can only respond in Russian https://www.youtube.com/watch?v=Smn8CFhV3Mg
Seriously, though, i wonder why would Russia be developing coronavirus vaccine if most people these days die there from "atypical pneumonia" and not from coronavirus ... at least if one is to believe the official info.
Seriously, though, i wonder why would Russia be developing coronavirus vaccine if most people these days die there from "atypical pneumonia" and not from coronavirus ... at least if one is to believe the official info.
Stock market is reacting very positively to this vaccine. The journal paper and health analysts consider immune response to be significant after booster and side effects relatively minor in all participants. Yet here you're quoting a Twitter posts that is brought to the top of the discussion on HN despite being not a primary or secondary, but a tertiary source.
> Stock market is reacting very positively to this vaccine.
The stock market should be considered because of why?
The stock market should be considered because of why?
Because some people have this idea that the stock market is able to perfectly understand risk in all situations to the point that it can be used to make decisions itself.
I’m not sure what to say here other then. A fool and their money will soon be parted.
I personally don’t know anyone that holds that opinion as you stated above .
Because of your use of the words "some people" and "perfectly" I'm reading your comment as sarcasm.
If you honestly believe that, I certainly hope you’re not actively trading the market!
In many cases, that's correct - but not when the issue is emotional and outside the normal investor field of expertise.
Because it makes us a lot of money.
While the paper and analysts are certainly good signs, can we say the same for the stock market? I thought the last little while was proof that it's fairly detached from real world conditions. As of late it seems to be responding to optimism more than anything concrete.
> Stock market
What in Gods name does the Stock market have to do with anything? This is peoples lives we are talking about, not $company share price.
What in Gods name does the Stock market have to do with anything? This is peoples lives we are talking about, not $company share price.
The author of that article also writes these fascinating articles "Things I won't work with"
https://blogs.sciencemag.org/pipeline/archives/category/thin...
https://blogs.sciencemag.org/pipeline/archives/category/thin...
Derek Lowe's base blog is better, and more active, currently: https://blogs.sciencemag.org/pipeline/
“But one thing that you do notice as you look over the data was that day 43 was the best – there was a further evaluation at day 57, and all three groups had gone down a bit in just those two weeks.“
Interesting that it was slightly weaker at day 57.
If people don’t gain permanent immunity once they get covid, will this sort of drug still work?
Interesting that it was slightly weaker at day 57.
If people don’t gain permanent immunity once they get covid, will this sort of drug still work?
A big question is how long it’ll last: if you got a yearly shot like the flu, that might be enough to prevent widespread outbreaks even if it doesn’t go away and people who are immune compromised still have to worry.
The other would be whether it helps with partial immunity: it doesn’t need to be lifelong immunity to be worth using if, say, it shifted the serious case rate down by a fair margin.
The other would be whether it helps with partial immunity: it doesn’t need to be lifelong immunity to be worth using if, say, it shifted the serious case rate down by a fair margin.
Given that Coronavirus mutation rates are orders of magnitude lower than influenza viruses, a yearly shot is unlikely.
How did you come to this conclusion? I’ve been curious about it for some time but haven’t seen anything concrete which could explain this at a level I understand.
Mutation is not the only factor determining how often a vaccine would be given. If antibodies only last a year from the vaccine dose, it should still be given yearly, even if the virus has not mutated.
I wasn’t referring to that but simply the concern that immunity might be relatively short lived: given how well this spreads even a vaccine which only gave, say, 10-12 months might be worthwhile if it meant that we could have schools, transit, restaurants, bars, churches, etc. able to operate normally.
It won’t be optimal, but if you stockpile enough and then administer it all at once, it effectively grants herd immunity for about two months, and the virus isn’t able to transmit during that time. Two months is longer than the incubation period of the virus. So you see where this is going.
Now if it isn’t close to 100% effective then you’ll probably still need people to quarantine, so, good luck with that.
Now if it isn’t close to 100% effective then you’ll probably still need people to quarantine, so, good luck with that.
I thought immunity wasn't a perfect correlation with presence of antibodies.
If enough people take the vaccine with that expected length of protection, it would certainly tamp down the spread at minimum. So it might still 'work' by collective standards.
40% of vaccine recipients experienced fever after administration. I'm not sure people would rush to take the vaccine with those odds, if only a few months of immunity is conveyed. There's a psychological element to this beyond whatever the science shows.
The most significant safety issues with this vaccine specifically regard the 250ug dose, which was not used in Phase 2 and won't be used in Phase 3.
As long as it's not a Grade 3 fever, I don't see a problem: many vaccines can cause (transient) fevers. (Part of that is due to the adjuvants used to prime the immune system by causing a localized inflammation).
I got a shot for the yellow fever a few years ago and I felt quite bad for a couple of days. When I was asked for a booster shot for measles, I was warned of the possibility of developing fever for a couple of days as well.
As long as it's not a Grade 3 fever, I don't see a problem: many vaccines can cause (transient) fevers. (Part of that is due to the adjuvants used to prime the immune system by causing a localized inflammation).
I got a shot for the yellow fever a few years ago and I felt quite bad for a couple of days. When I was asked for a booster shot for measles, I was warned of the possibility of developing fever for a couple of days as well.
Similarly, children very often get fevers after some of their first vaccines. It's no big deal.
Any time you take your kids to get immunized they tell you the spiel about "Expect xoreness and swelling at the site, fever up to xxx for three days. If it lasts longer we need to see them back"
Discomfort is totally expected with vaccines.
Discomfort is totally expected with vaccines.
Vaccines aren't completely harmless, but this would be expected. You can do a self test with a flu vaccine. Your doctor probably will recommend no exhausting activities for a few days after taking the shot. If you, for science, ignore that advice, you might feel quite horrible.
Every time I get the flu shot it feels like someone punched me hard on the shoulder where it was administered for a couple days, and I feel generally unwell (but not 'bad' per-se).
But the alternative is I could end up in the ICU with pneumonia without it (and have, in the past, from the flu), so the risk/annoyance is worth it.
But the alternative is I could end up in the ICU with pneumonia without it (and have, in the past, from the flu), so the risk/annoyance is worth it.
My experience with DTP shots is that one of my arms is a useless-but-painful dead weight for a week or so. I'd still take that over getting tetanus.
Perhaps I should rephrase it, didn't want to make it sound like getting vaccinated is a bad idea. It does activate your immune system though and that can make you feel really unwell. Fever is not a disease, it is an immune response. But those can still induce complications. Doctors won't administer a shot if you already have pneumonia for these reasons.
I felt absolutely nothing.
I used to administer flu shots as an Army medic back in the day. I don't recall ever receiving or giving this warning.
Kids especially frequently get fever after vaccines. It's very common.
I'm a generally healthy 30-something and I always get a reaction from a flu shot - fever, swollen lymph node, pain
The worst I've gotten from a flu shot is mild muscle discomfort at the injection site for the first 24h.
Does that actually happen to people? I thought it wasn't too common. My family gets this warning every year when we get our shots, but we never experience any of those effects. My kids complain about the arm pain, but even I don't get that part of it. Nothing changes for me after getting the flu vaccine (other than the protection of course).
Just to be clear I do HIIT, strength training, and (my favorite) lots of yard work regularly and the flu vaccine doesn't interfere with any of that.
Just to be clear I do HIIT, strength training, and (my favorite) lots of yard work regularly and the flu vaccine doesn't interfere with any of that.
I've never heard the exhausting activities warning, but I do get mild flu-like symptoms for a few days (low grade fever, some fatigue, congestion) after the flu shot most years.
I don't know how common it is to experience this, as I would say I have a subpar immune system (frequently sick as a kid, history of food allergies, etc.). But when I've discussed it with doctors they do say my reaction is unsurprising, however the benefits outweigh the "costs".
I don't know how common it is to experience this, as I would say I have a subpar immune system (frequently sick as a kid, history of food allergies, etc.). But when I've discussed it with doctors they do say my reaction is unsurprising, however the benefits outweigh the "costs".
Oh, yes, I have seen that very often. Symptoms are nearly the same as getting the flu. The type of vaccine, live or inactivated, is relevant though, but it can happen with both. Your immune system is weakened for a time until you have produced. Moderate training is no problem though, perhaps even helpful, but exhausting yourself can lead to problems.
I feel like the psychological element goes the other way, at least for me.
In January, this would have felt like a terrible deal. Right now, it feels like you're telling me that - should I socially isolate for a few weeks a year after vaccine shots - I can largely go back to living a normal life. That feels great.
In January, this would have felt like a terrible deal. Right now, it feels like you're telling me that - should I socially isolate for a few weeks a year after vaccine shots - I can largely go back to living a normal life. That feels great.
Why would isolation be required after taking the vaccine? You should be able to resume normal life as soon as you’re well enough, right?
Fair. I think that the "sick with Covid == stay at home" link is strong enough in my brain I'm just assuming you'd want to stay home with even the vaccine, but that's not something really based in scientific fact.
Couldn't you have gotten the disease shortly before vaccination and potentially be contagious for some period afterwards?
The simple act of producing the vaccine and then administering it would take much longer than a few months.
I believe we are fast-tracking production of several vaccines on the assumption that they might work. So even though testing is still going on, currently producing them just in case.
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They begin the manufacturing process of the vaccine well before it even finishes phase 3 testing.
That will partly depend on how it's rolled out. If we coordinate and get lots of people the vaccine in a short amount of time, then it will help a lot because we'll get the effect of herd immunity. If it only gets to a few people at a time, it will help less.
It also depends on the efficiency of the second round. If it works great the first time you get the shots, but when it wears off and you get a second round it doesn't work as well that is bad.
From the original article, it sounds like the first round is only minimally effective, and the major boost comes from the second round.
This is a confusing area. The two shots are part of round one. When that wears off and you get more (which might be 2 more shots) that is the next round.
If english has a good way to say this I'm not aware of it.
If english has a good way to say this I'm not aware of it.
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AZD1222 vaccine by Oxford and AstraZeneca looks the most promising so far:
+ already in late-stage trials
+ they are pre-producing it at large capacity
+ verified safe, no side-effects
~ may be very efficient in preventing diseases, but not enough to prevent spread, just slows it
~ may need second shoot after 4 months
~ long-term immunity is questionable for covid and you can get only two shoots of this type of vaccine in lifetime while maintaining it efficiency
https://www.nytimes.com/2020/04/27/world/europe/coronavirus-...
+ already in late-stage trials
+ they are pre-producing it at large capacity
+ verified safe, no side-effects
~ may be very efficient in preventing diseases, but not enough to prevent spread, just slows it
~ may need second shoot after 4 months
~ long-term immunity is questionable for covid and you can get only two shoots of this type of vaccine in lifetime while maintaining it efficiency
https://www.nytimes.com/2020/04/27/world/europe/coronavirus-...
> + verified safe, no side-effects
I'm not a doctor and there's a good chance I'm missing something, but this seems crazy to me. How could this be known already? I could understand if it just means that short term side-effects are rare to nonexistent, but what about long term issues or rare catastrophic ones?
I'm not a doctor and there's a good chance I'm missing something, but this seems crazy to me. How could this be known already? I could understand if it just means that short term side-effects are rare to nonexistent, but what about long term issues or rare catastrophic ones?
Can you please explain the last bullet or post a link?
"~ long-term immunity is questionable for covid and you can get only two shoots of this type of vaccine in lifetime while maintaining it efficiency"
This suggests some fundamental misunderstanding in how I think about the immune system (which is unsurprising given I have no formal background there), and I think I'd learn a lot of important things from understanding why or how this works.
If it's hard or deep, I'm glad to do long-form reading if you have a link.
"~ long-term immunity is questionable for covid and you can get only two shoots of this type of vaccine in lifetime while maintaining it efficiency"
This suggests some fundamental misunderstanding in how I think about the immune system (which is unsurprising given I have no formal background there), and I think I'd learn a lot of important things from understanding why or how this works.
If it's hard or deep, I'm glad to do long-form reading if you have a link.
The Oxford vaccine (ChAdOx1) uses another vector virus called the adenovirus to deliver the coronavirus genes which the body can fight against. The issue is that some people might have pre-existing immunity to the adenovirus, making the vaccine ineffective. Since ChAdOx1 uses an adenovirus which infects chimpanzees, it is likely that most people will not have any pre-existing immunity to the vector virus. I guess the parent comment is referring to the fact that the body might develop immunity to the chimpanzee vector virus after two doses, making booster shots ineffective.
Thank you!
I'm currently enrolled in the only currently active phase III trial for a COVID-19 vaccine developed by Oxford Unviersity. https://www.ovg.ox.ac.uk/news/covid-19-vaccine-development
It's supposedly a "front-runner" but also who knows!
It's supposedly a "front-runner" but also who knows!
How frequently do you get tested for the virus?
Weekly with a PCR swab.
2-monthly for antibodies via a blood sample.
That is pretty cool. I have so many questions, but you are not obligated to answer ;). How old are you? Did you experience any side effects from the vaccine? Are you a mask wearer? Do you go out in public as others have?
I'm 29.
I suffered standard vaccine side-effects. Flu-like symptoms for a couple of hours, muscle aches, that sort of thing. All resolved within 3 days but I had to self-isolate for those 3 days as having a fever in the UK means you must stay at home.
I wear a mask in crowded places and shops.
I go out in public, as normal but I work from home. I'm an otherwise healthy volunteer, so my risk of being severely unwell is _relatively_ low.
It's worth bearing in mind that the control group got an active vaccine for Meningitis, so it's impossible to know if I'm protected, and even if I was vaccinated with the experimental vaccine, if it even works!
Happy to answer other questions too :)
I suffered standard vaccine side-effects. Flu-like symptoms for a couple of hours, muscle aches, that sort of thing. All resolved within 3 days but I had to self-isolate for those 3 days as having a fever in the UK means you must stay at home.
I wear a mask in crowded places and shops.
I go out in public, as normal but I work from home. I'm an otherwise healthy volunteer, so my risk of being severely unwell is _relatively_ low.
It's worth bearing in mind that the control group got an active vaccine for Meningitis, so it's impossible to know if I'm protected, and even if I was vaccinated with the experimental vaccine, if it even works!
Happy to answer other questions too :)
This NY Times overview of various candidate vaccines is interesting:
https://www.nytimes.com/interactive/2020/science/coronavirus...
Coronavirus Vaccine Tracker
https://www.nytimes.com/interactive/2020/science/coronavirus...
Coronavirus Vaccine Tracker
I also like BioRender's, which also tracks drug treatments and links to the individual trials: https://biorender.com/covid-vaccine-tracker
Oh wow! Thanks for this. I didn't know there were candidates in Phase III already or that there's already a vaccine that's been approved.
It is approved only for use within the Chinese military.
It's also unlikely to be very effective due to it using the adenovirus Ad5 as a vector, which is a human adenovirus that many people have antibodies against. This means a marked loss of efficacy if you have them.
Well, the trials show that is effective in essentially everyone. The use of the Ad5 vector does not require replication, it's therefore unlikely that antibodies will be effective at stopping a significant amount of the vector implantation of a large fraction of the viral particles in cells.
If you read the study, it states that even in recipients with high Ad5 immunity, as long as the dose is sufficient (high-dose or medium dose) long-term seroconversion is high - 84% to 100% in medium or high dose after 28 days for recipients with strong antibodies against Ad5, and for high-dose seroconversion and interferon gamma response was indistinguishable from those without strong Ad5 immunity. [0, fig 1 - Specific T-cell response measured by ELISpot].
So I don't really think it will be an issue. You just need the proper dose. : https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
If you read the study, it states that even in recipients with high Ad5 immunity, as long as the dose is sufficient (high-dose or medium dose) long-term seroconversion is high - 84% to 100% in medium or high dose after 28 days for recipients with strong antibodies against Ad5, and for high-dose seroconversion and interferon gamma response was indistinguishable from those without strong Ad5 immunity. [0, fig 1 - Specific T-cell response measured by ELISpot].
So I don't really think it will be an issue. You just need the proper dose. : https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
Like with Moderna, if I recall (on mobile, so I can't refresh my memory by rereading it) the highest doses had some Grade 3 level fevers. So probably medium dose would be used.
Yep, side effects seem to be comparable. Medium dose would probably be used, or likely something between medium dose and high dose.
Note Moderna's vaccine is using newish technology in that rather than being injected with bits of the virus, dead virus or attenuated virus, so your body can mount an immune response, you are given RNA which encodes the bit of the virus - so your body makes the virus bit itself, which then leads to the immune response.
How this compares to the other approaches will be interesting.
How this compares to the other approaches will be interesting.
For the record, other companies are having (early) success with RNA too.
BioNTech https://investors.biontech.de/news-releases/news-release-det...
CureVac https://www.curevac.com/news/curevac-s-optimized-mrna-platfo...
BioNTech https://investors.biontech.de/news-releases/news-release-det...
CureVac https://www.curevac.com/news/curevac-s-optimized-mrna-platfo...
Very interesting but an ELI5 of the implications would be welcome:
Okay it needs 2 injection. Do they need to be spaced by 42 days? If so that would induce nuisible inertia.
How many percents of the patients recovered from the covid thanks to to the injection? I see 80% of response but I don't know how that translate into chance de of curing. Also how fast did they recover? The second injection has an adverse response, how bad is it? Too much for mainstream?
It's always fascinated me, this paradox of reporting: The author has made a lot of researchs and a great write-up but fail to answer the most pressing questions that both mainstream people and shareholders wants!
Okay it needs 2 injection. Do they need to be spaced by 42 days? If so that would induce nuisible inertia.
How many percents of the patients recovered from the covid thanks to to the injection? I see 80% of response but I don't know how that translate into chance de of curing. Also how fast did they recover? The second injection has an adverse response, how bad is it? Too much for mainstream?
It's always fascinated me, this paradox of reporting: The author has made a lot of researchs and a great write-up but fail to answer the most pressing questions that both mainstream people and shareholders wants!
On the linked Twitter thread from the article there is a link to the AE chart
https://twitter.com/RNAiAnalyst/status/1283149377427701761/p...
https://twitter.com/RNAiAnalyst/status/1283149377427701761/p...
Thanks! I would love to see a similar chart of competing vaccines.
So the side effects are huge relative to standard vaccines but rationally, if it works everybody should still take it. This will need to be enforced by politicians as I doubt people would have the maturity to take it voluntarily. It's the kind of wicked problem where we want that everybody take it except ourselves
So the side effects are huge relative to standard vaccines but rationally, if it works everybody should still take it. This will need to be enforced by politicians as I doubt people would have the maturity to take it voluntarily. It's the kind of wicked problem where we want that everybody take it except ourselves
>So the side effects are huge
Those side effects are very mild. Headache. Myalgia. etc.
How many times in your life has your arm been sore after a flu shot? These need to be measured but are not 'huge side effects'. No observed adverse event met the pre-defined cutoffs for stopping the trial.
Those side effects are very mild. Headache. Myalgia. etc.
How many times in your life has your arm been sore after a flu shot? These need to be measured but are not 'huge side effects'. No observed adverse event met the pre-defined cutoffs for stopping the trial.
The two injections are mostly due to safety protocols.
Human challenge studies need to be seriously lined up right now as a part of phase III work. (Human challenge studies mean giving people the full vaccine dose, checking for antibodies, then giving a dose of the actual disease).
The consensus seems to be "they are not ethical", which is an extreme, beaucratic, twisted set of ethics.
Small challenge studies of 100 people, who have a low risk profile, who volunteer to help their friends, family, and humanity will give us a lot of confidence to move forward.
The fatality rate of a soldier volunteering in the US for world war Ii was about 2%. For young healthy volunteers, we are talking something like 2 orders of magnitude less risk, for more clear marginal benefit than being one extra soldier in a war.
I feel that this isn't being lined up is negligent insanity.
(If you want to volunteer without any commitment https://1daysooner.org/ - no affiliation although I volunteered).
The consensus seems to be "they are not ethical", which is an extreme, beaucratic, twisted set of ethics.
Small challenge studies of 100 people, who have a low risk profile, who volunteer to help their friends, family, and humanity will give us a lot of confidence to move forward.
The fatality rate of a soldier volunteering in the US for world war Ii was about 2%. For young healthy volunteers, we are talking something like 2 orders of magnitude less risk, for more clear marginal benefit than being one extra soldier in a war.
I feel that this isn't being lined up is negligent insanity.
(If you want to volunteer without any commitment https://1daysooner.org/ - no affiliation although I volunteered).
Remember that is just the risk of death.
My wife is young (40 yo) fit and healthy, and 115 days after contracting covid she is still ill with post covid symptoms - there is no way she could work still and cannot look after or even play with our kids.
On her post covid support group it mainly seems to be women over 40 and men from 20 to 50 - though only about 7000 people who self selected to join the group so that might not be representative.
Just saying that while risk of death are low, there are other risks - though as yet poorly understood and researched.
My wife is young (40 yo) fit and healthy, and 115 days after contracting covid she is still ill with post covid symptoms - there is no way she could work still and cannot look after or even play with our kids.
On her post covid support group it mainly seems to be women over 40 and men from 20 to 50 - though only about 7000 people who self selected to join the group so that might not be representative.
Just saying that while risk of death are low, there are other risks - though as yet poorly understood and researched.
I had this experience, though with a different virus. It’s no joke. I was in above average shape, able to run fast and far, lift heavy things, free dive deep and long, etc. After a two week illness, I couldn’t lift my hands above my head and I haven’t run more than 10km since, let alone at <5m per km. It has been 4 years. It wrecked my lungs and I think even caused mild nerve damage.
If COVID is doing similar things to people, it’s very serious. It’s potentially life altering. I genuinely suspect I will never be as healthy or as strong as I was. I didn’t believe this could happen to healthy people in their 20s, especially not someone who could run a half marathon on a whim, but humans simply aren’t invulnerable.
If COVID is doing similar things to people, it’s very serious. It’s potentially life altering. I genuinely suspect I will never be as healthy or as strong as I was. I didn’t believe this could happen to healthy people in their 20s, especially not someone who could run a half marathon on a whim, but humans simply aren’t invulnerable.
So sorry to hear that - the more we have read about the post viral issues from SARs, ebola and the 'spanish flu', the more we see that there are a huge number of people affected in very different ways. For the first 3 months we totally felt disbelieved by doctors and even some friends - 'are you sure it isn't just anxiety?'.
Slowly doctors are realising that while the majority do recover, a not insignificant group will be affected for a lager period of time. Total guess but even if the number of long term cases is the same as those that die, and if on average they can't work for 6 months (conservative) then the economic impacts on those people and their families can be huge.
I really hope you see light at the end of the tunnel and take it easy.
Slowly doctors are realising that while the majority do recover, a not insignificant group will be affected for a lager period of time. Total guess but even if the number of long term cases is the same as those that die, and if on average they can't work for 6 months (conservative) then the economic impacts on those people and their families can be huge.
I really hope you see light at the end of the tunnel and take it easy.
Thank you, and likewise - I hope your wife continues to recover and it doesn’t impact your family too much.
I think the reality of sickness is often a revelation once it happens. It’s hard to believe what an impact it can have, seemingly arbitrarily. But with the right support and the right state of mind, recovery is often possible despite being difficult. After a point it just doesn’t happen on its own. It’s another part of life, something to learn from I suppose.
I think the reality of sickness is often a revelation once it happens. It’s hard to believe what an impact it can have, seemingly arbitrarily. But with the right support and the right state of mind, recovery is often possible despite being difficult. After a point it just doesn’t happen on its own. It’s another part of life, something to learn from I suppose.
Just to add to your excellent post, the same mistake happens with war casualties. A war might kill "only" 2% of the soldiers, but for every soldier killed there are many who suffer significant physical and/or mental harm that impacts the rest of their life.
If the challenge trial is done properly (i.e. with a representative sample of the population) then wouldn't all risks - both known and not-yet-known - apply to both the trial participants as well as the general population?
Agree - just with the trial you will have a 100 percent chance or being exposed directly to the virus. Not saying the risk isn't worth taking, just that the only risk is not death.
Sounds like we're well on our way to having a 100% chance of being directly exposed anyway.
Sadly I agree - though we've got to remember it is possible to get this virus and the transmission under control - plenty of places are winning the battle - it just takes will and coordination. But something every country has currently...
So, long story short: encouraging first phase, with a whole lot of caveats, it will need to wait on phase 2 and phase 3 even if everything goes well, there are some negative reactions (but in this small group nothing too serious), and it would take at least two doses and the effect starts to fade after a couple months (which doesn't mean it would go away entirely). Plus we really only know that there was _some_ response, not that it would protect you in the way we normally expect a vaccine to.
In other words, long story short, probably not this year.
In other words, long story short, probably not this year.
> In other words, long story short, probably not this year.
Moderna aims at an emergency use authorization for health personnel in October or during the autumn in general if the interim data from Phase II / III is good enough.
Moderna aims at an emergency use authorization for health personnel in October or during the autumn in general if the interim data from Phase II / III is good enough.
I would not be surprised if there were something like that happening, although even that would be a best case. When I said "not this year", I meant it's not going to meaningfully impact the course of the pandemic this year. If they do manage to get something to protect the most at-risk health personnel this year, that would be awesome. I wouldn't count on it.
* Plus we really only know that there was _some_ response, not that it would protect you in the way we normally expect a vaccine to.*
I don't understand, did the tested patients recovered from covid? They did not inject on them the virus in order to test the vaccine? So many people die and we're too shy to test volunteers? So many humans on earth would risk their lives for a few hundred dollars, it is the reality where we live in. Let's take advantage of this reality, give them more than they would expect + glory and so much more lives would be saved. By doing heuristic guessing of if the vaccin works without really testing it we're going to do order of magnitude more harm to humanity.
I don't understand, did the tested patients recovered from covid? They did not inject on them the virus in order to test the vaccine? So many people die and we're too shy to test volunteers? So many humans on earth would risk their lives for a few hundred dollars, it is the reality where we live in. Let's take advantage of this reality, give them more than they would expect + glory and so much more lives would be saved. By doing heuristic guessing of if the vaccin works without really testing it we're going to do order of magnitude more harm to humanity.
Unfortunately there have been many, many deaths and also populations left disfigured and disabled from reckless medical experimentation. That is why there are such strict rules now.
Phase I is just safety ( and a bit of dose range finding ) - does the drug/treatment/vaccine harm or kill people on it's own - small number of people, with varying doses - ideally starting at the low end. You will do some tests to see if you get the expected biological response as a surrogate for efficacy.
Phase II is where you start looking at if it works ( while still looking at safety- always looking at safety ), here you are also trying to typically work out what is the right dosing regime ( how much, how often ).
Phase III is large enough numbers to get population level stats for safety and efficacy, given the treatment regime you have decided on.
Also you don't just need willing people to take the vaccine to do a proper trial, you need the medical infrastructure around it.
People to administer it, keep track of the patients - monitoring them for any signs of adverse reaction - reliable people to take blood samples and handle them properly, proper note and record keeping etc.
The other thing to consider in trials is that roughly half your patients don't get anything ( more accurately a placebo ) - and in the case of vaccine trials, you need to control group to get infected!!! Otherwise you can't see any protective value.
You'd need to choose you control group to carefully reflect the test group - if you had your vaccine test group in New Zealand and your control group in the US - nobody would believe your result.
At the moment people doing trials in America have an advantage in that the virus is still infecting lots of people, so you can more easily demonstrate protection. If you are trying to trials in China - pretty hard.
I don't think lack of volunteers is the problem. If you want to do it ethically, you have to do it incrementally.
Phase II is where you start looking at if it works ( while still looking at safety- always looking at safety ), here you are also trying to typically work out what is the right dosing regime ( how much, how often ).
Phase III is large enough numbers to get population level stats for safety and efficacy, given the treatment regime you have decided on.
Also you don't just need willing people to take the vaccine to do a proper trial, you need the medical infrastructure around it.
People to administer it, keep track of the patients - monitoring them for any signs of adverse reaction - reliable people to take blood samples and handle them properly, proper note and record keeping etc.
The other thing to consider in trials is that roughly half your patients don't get anything ( more accurately a placebo ) - and in the case of vaccine trials, you need to control group to get infected!!! Otherwise you can't see any protective value.
You'd need to choose you control group to carefully reflect the test group - if you had your vaccine test group in New Zealand and your control group in the US - nobody would believe your result.
At the moment people doing trials in America have an advantage in that the virus is still infecting lots of people, so you can more easily demonstrate protection. If you are trying to trials in China - pretty hard.
I don't think lack of volunteers is the problem. If you want to do it ethically, you have to do it incrementally.
Are you referring to the subjects injected with the experimental vaccine? A phase I trial's purpose is to see if the drug is safe for humans and get an idea of what the best dose is, not if it's effective. As to deliberately exposing people to the coronavirus, that's an ethical mess. The parent blog's author has another post that covers this as well [0].
tl;dr (the blog in general is a great resource though):
* We're not at a point where we need to deliberately expose people, as there's enough people being exposed in their communities.
* The normal standard for those deliberate tests also only recommend it if there's known effective for treatments for the diseases, which (obviously) there is not for COVID-19. Hell, we're still figuring out what exactly it's doing in the body.
* As a sibling comment brings up, history is riddled with unethical medical experimentation. We don't want to repeat those mistakes.
0: https://blogs.sciencemag.org/pipeline/archives/2020/07/02/ch...
tl;dr (the blog in general is a great resource though):
* We're not at a point where we need to deliberately expose people, as there's enough people being exposed in their communities.
* The normal standard for those deliberate tests also only recommend it if there's known effective for treatments for the diseases, which (obviously) there is not for COVID-19. Hell, we're still figuring out what exactly it's doing in the body.
* As a sibling comment brings up, history is riddled with unethical medical experimentation. We don't want to repeat those mistakes.
0: https://blogs.sciencemag.org/pipeline/archives/2020/07/02/ch...
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So, easy now. The phase 1/2/3 process has been developed over a long period of time, and has given good results. There are doubtless a lot of ways to do it worse. Deciding to make up a new process on the spot in the middle of a crisis, with a lot of high-anxiety thinking, may not actually deliver a quicker/better result. Plus, the manufacturing is going to be started in parallel with the testing, but we don't have the capacity to manufacture every one of the dozens of vaccines that are in development right now, so which ones do we make "risk starts" on? Well the best way to guess would be to look at the phase 1/phase 2 results, and see which seem most promising.
There are a lot more ways to get it wrong, than to get it right, and we want the quickest, good result, not just the quickest result. Aside from the ethical consequences of experimenting on poor people (and I don't think those are something we should put aside), coming up with a new process on the spot is not even probably the best way to get a good result fast. Would the people who step forward to do that be unusually healthy (hence willing to take the risk), and so throw off the results? Would they be disproportionately people who have already had Covid-19, for the same reason? Would they be different in some other way? Let's not try to wing this. We've got a time-and-battle-tested method for developing a vaccine. I would prefer we use that.
There are a lot more ways to get it wrong, than to get it right, and we want the quickest, good result, not just the quickest result. Aside from the ethical consequences of experimenting on poor people (and I don't think those are something we should put aside), coming up with a new process on the spot is not even probably the best way to get a good result fast. Would the people who step forward to do that be unusually healthy (hence willing to take the risk), and so throw off the results? Would they be disproportionately people who have already had Covid-19, for the same reason? Would they be different in some other way? Let's not try to wing this. We've got a time-and-battle-tested method for developing a vaccine. I would prefer we use that.
Why should only the financially desperate be asked to sacrifice for their species? What a repugnant stance you've adopted.
You can randomize it in an authoritarian way if you reject here the free market, the way of selection matter far less than the discussion of how much lives could be saved.
What a repugnant stance you've adopted. Thinking like you think is consenting to mass murder, do you realize it ?
Here's my calculus: The phase I trial has approximately lasted 2 months. I checked the number of total deaths from 01 may to 01 July -> https://www.worldometers.info/coronavirus/worldwide-graphs/#...
This give us 277,145 human deaths in this trial period. According to https://en.wikipedia.org/wiki/Mortality_due_to_COVID-19#Mort... mortality rate for a ~20 years old should be at least lower than 0.1%.
With all those data in mind, here's the reasoning: The metric of effectiveness for this Moderna vaccine candidate is epistemologically LOW. They use fuzzy heuristics of matching approximately the immune response of naturally recovering patients as a claim of being effective. So firstly this reasoning is simplistic especially since researchers do not understand precisely how the working immune response work. So there is a risk of the vaccine to be a disappointment. If it is, those 277,145 human lifes would have been wasted and far more will die until we find the true vaccin. But what you need to understand is that researchers are condemned to match the existing immune response as otherwise, without testing on infected young humans, they cannot predict the vaccine expected performance. This alone is far enough for defending that they should have tested on a few dozen of infected patients the effectiveness. If they did: two possible scenarios: (lets suppose they tested 30 humans in their twenties that would make 0.3% of chance of deaths (comparatively to 277,145 human deaths) and the likelihood would be actually far lower as they would be actively monitored) scenario A) the vaccine doesn't work and it shows empirically, it save them weeks of evidence and therefore make them reconsider another paradigm for the virus. That alone would save at the very least thousands of lives by allowing the true vaccine to be found earlier. So you must realize that your "repugnant stance" of inaction is responsible in this likely scenario of far more deaths, sadly numbers quickly become unproportional to the emotional empathic response for a homo sapiens, this kind of brain failure honestly give a taste of vomit in my mouth, but yeah everybody is victim of this cognitive bias, even myself so no offense. In the second scenario, the empiricism would show them that their vaccine works: here again it would accelerate the delivery, and crucially the data would give them insights and allow for far better fine tuning of how the vaccine works and the optimal dosage. Is is not unreasonable to think that such speedup would allow to save a similar order of magnitude than 277,145 human deaths but could actually be far more (imagine 6 months of work saved y avoiding empirically invalidated or fine tuned research directions ? Even if it were to be lower, even if the data sped up the research by only one day (an insanely pessimistic view that I only show to defend your reasoning to the extreme, to its limit) would still save more than 5000 lives which is indeed far bigger than the likely lower than 0.3% of death rate for ~30 persons, so even in the ridiculous limit we talk about 5000+ vs 0.3 death.
What a repugnant stance you've adopted. Thinking like you think is consenting to mass murder, do you realize it ?
Here's my calculus: The phase I trial has approximately lasted 2 months. I checked the number of total deaths from 01 may to 01 July -> https://www.worldometers.info/coronavirus/worldwide-graphs/#...
This give us 277,145 human deaths in this trial period. According to https://en.wikipedia.org/wiki/Mortality_due_to_COVID-19#Mort... mortality rate for a ~20 years old should be at least lower than 0.1%.
With all those data in mind, here's the reasoning: The metric of effectiveness for this Moderna vaccine candidate is epistemologically LOW. They use fuzzy heuristics of matching approximately the immune response of naturally recovering patients as a claim of being effective. So firstly this reasoning is simplistic especially since researchers do not understand precisely how the working immune response work. So there is a risk of the vaccine to be a disappointment. If it is, those 277,145 human lifes would have been wasted and far more will die until we find the true vaccin. But what you need to understand is that researchers are condemned to match the existing immune response as otherwise, without testing on infected young humans, they cannot predict the vaccine expected performance. This alone is far enough for defending that they should have tested on a few dozen of infected patients the effectiveness. If they did: two possible scenarios: (lets suppose they tested 30 humans in their twenties that would make 0.3% of chance of deaths (comparatively to 277,145 human deaths) and the likelihood would be actually far lower as they would be actively monitored) scenario A) the vaccine doesn't work and it shows empirically, it save them weeks of evidence and therefore make them reconsider another paradigm for the virus. That alone would save at the very least thousands of lives by allowing the true vaccine to be found earlier. So you must realize that your "repugnant stance" of inaction is responsible in this likely scenario of far more deaths, sadly numbers quickly become unproportional to the emotional empathic response for a homo sapiens, this kind of brain failure honestly give a taste of vomit in my mouth, but yeah everybody is victim of this cognitive bias, even myself so no offense. In the second scenario, the empiricism would show them that their vaccine works: here again it would accelerate the delivery, and crucially the data would give them insights and allow for far better fine tuning of how the vaccine works and the optimal dosage. Is is not unreasonable to think that such speedup would allow to save a similar order of magnitude than 277,145 human deaths but could actually be far more (imagine 6 months of work saved y avoiding empirically invalidated or fine tuned research directions ? Even if it were to be lower, even if the data sped up the research by only one day (an insanely pessimistic view that I only show to defend your reasoning to the extreme, to its limit) would still save more than 5000 lives which is indeed far bigger than the likely lower than 0.3% of death rate for ~30 persons, so even in the ridiculous limit we talk about 5000+ vs 0.3 death.
What is the error rate of the immune system response currently used, compared to actual immune response? If it is small, then the value of infecting humans directly goes way down. Further, what is the probability that the control group and the vaccine groups will not be exposed naturally and accidentally to Covid19 during the Phase II, Phase III studies? If they are likely to be accidentally exposed, then purposefully exposing them has even less value. Given the current infection rates in the US, this likelihood seems pretty good.
The 277,145 number is meaningless. The vaccine was not known to help in any way 2 months ago. For all we knew at the time, if we had started giving this to people on mass 2 months ago, we would have had 300k deaths from the vaccine by now.
Then, the vaccine is not yet known to be effective. We only have proof that it is safe, but we don't have rigorous control studies showing that it is effective yet (we need the Phase II & III trials for that). Before that, there is only a "hunch" that it will help at all, so taking death numbers for the next few months is also going to be meaningless.
Finally, your "even if the data sped up the research by only one day" calculation is pure sophism. Why not assume that the data could slow down the research? What if one of the patients dies because of complications after being infected, and that affects team morale, slowing down the research? What if one of the researchers accidentally gets sick themselves because of improper handling of the live virus, again slowing down the research?
The final point is: we are already rushing this. There are good reasons we have stopped testing drugs on volunteers, we have a horrible history behind us of the effects, often without much better results (and often much worse results) than current methods. There methods we have for estimating actual immunity based on immune system response have been studied for some time and are considered good. Putting people's lives in danger is needless complication, more likely to slow everything down than to speed it up.
The 277,145 number is meaningless. The vaccine was not known to help in any way 2 months ago. For all we knew at the time, if we had started giving this to people on mass 2 months ago, we would have had 300k deaths from the vaccine by now.
Then, the vaccine is not yet known to be effective. We only have proof that it is safe, but we don't have rigorous control studies showing that it is effective yet (we need the Phase II & III trials for that). Before that, there is only a "hunch" that it will help at all, so taking death numbers for the next few months is also going to be meaningless.
Finally, your "even if the data sped up the research by only one day" calculation is pure sophism. Why not assume that the data could slow down the research? What if one of the patients dies because of complications after being infected, and that affects team morale, slowing down the research? What if one of the researchers accidentally gets sick themselves because of improper handling of the live virus, again slowing down the research?
The final point is: we are already rushing this. There are good reasons we have stopped testing drugs on volunteers, we have a horrible history behind us of the effects, often without much better results (and often much worse results) than current methods. There methods we have for estimating actual immunity based on immune system response have been studied for some time and are considered good. Putting people's lives in danger is needless complication, more likely to slow everything down than to speed it up.
Our immune systems are very complex and unique! If you want to apply scientific method and improve outcomes (safety, efficacy), then there is a lot more data to collect. Sharing that data and allowing recipients to own their data, would go a long way towards improving vaccine safety and allow for customization as needed. My children have had ~minor/moderate reactions to the varicella vaccine (fluid on my son's hip joint ~2" from injection site at 23 days--ER doctors just shrug), my daughter a moderate rash. How could these be improved? Guillain-Barre is very real side effect as well. How can it be avoided? I accumulate metals easily, so Al, a potent neurotoxin hangs out in my system much longer than others (possible/probable HLA variant). Shouldn't the adjuvant for my vaccines exclude Al?
Measuring temperature & physical symptoms is a good start. It would be great if these trials would measure each recipients HLA SNPs (see GSK MERS 2009 fiasco and others), T-cells (CD4/8/57/etc), inflammation markers like C3a,C4a,TGF-b, MMP-9, and cytokines like TNF-a -- before and after each vaccine dose. Measuring for all ingredients pre-post each dose is also important because the metabolization for each component is not uniform. Stop using 2010+ technology to make vaccines & medications and then evaluating the applied result with 1990s (or earlier) methods.
So if you want to shut up 'anti-vaxxers' than collect/share the data from everyone who receives a vaccine and improve the process instead of shrouding results or conducting half-assed studies (AstraZeneca using meningitis vaccine as control instead of true placebo).
Measuring temperature & physical symptoms is a good start. It would be great if these trials would measure each recipients HLA SNPs (see GSK MERS 2009 fiasco and others), T-cells (CD4/8/57/etc), inflammation markers like C3a,C4a,TGF-b, MMP-9, and cytokines like TNF-a -- before and after each vaccine dose. Measuring for all ingredients pre-post each dose is also important because the metabolization for each component is not uniform. Stop using 2010+ technology to make vaccines & medications and then evaluating the applied result with 1990s (or earlier) methods.
So if you want to shut up 'anti-vaxxers' than collect/share the data from everyone who receives a vaccine and improve the process instead of shrouding results or conducting half-assed studies (AstraZeneca using meningitis vaccine as control instead of true placebo).
Spending a bunch more time collecting data to convince people who reflexively put their fingers in their ears when presented with evidence seems a decidedly wrong-headed approach.
Spending time collecting data is for improving our understanding of an individual's immune system. Sharing that data helps educate those who are unfamiliar with, but have complete ownership of their body.
Data needs a narrative attached, otherwise it's just noise. There is a point where adding more data doesn't change the narrative, so it's pointless to continue gathering data.
Are the immune responses to the vaccine identical across the trial group? No. Is everyone's response to sars-cov-2 identical? No. Is everyone's immune system unique in its signaling and adaptive behavior? Yes. How is it possible to correlate immune responses by measuring 0.000x percent of the available data? We do not have complete understanding of our immune systems, thus we need more data and most of it can be relevant.
Ok, you can sit in a corner for the next 1000 years while all of that data is gathered for you. A glimpse at your username suggests you have intense bias with regards to the human body and its immune system.
I agree it doesn't make sense for the purpose of convincing anti-vaxxers. But I do think sometimes valuable research topics end up getting thrown out "with the bathwater" so to speak when the general public gets too wrapped up in a pseudoscientific interpretation (especially when that interpretation was originally supported by some poorly done or fraudulent published research).
For example, galvanic skin response was used for very bullshit purposes, which led to research on it essentially stopping for over a decade. But recently it has been rebranded as "electrodermal activity", and turns out to have use for studying Epilepsy as well as other promising potential use cases (such as improving sleep staging without EEG).
I am less aware of literature on side effects for current vaccines, so I don't know if this same phenomenon has happened. But I wouldn't be surprised if certain lines of thinking are reflexively stomped down right now.
Maybe this just needs to be the natural life cycle of science though, it might be for the greater good to let anti-vax die down before doing anything which could stoke their flames.
For example, galvanic skin response was used for very bullshit purposes, which led to research on it essentially stopping for over a decade. But recently it has been rebranded as "electrodermal activity", and turns out to have use for studying Epilepsy as well as other promising potential use cases (such as improving sleep staging without EEG).
I am less aware of literature on side effects for current vaccines, so I don't know if this same phenomenon has happened. But I wouldn't be surprised if certain lines of thinking are reflexively stomped down right now.
Maybe this just needs to be the natural life cycle of science though, it might be for the greater good to let anti-vax die down before doing anything which could stoke their flames.
I watched an interview with an individual who after receiving a tetanus shot developed transverse myelitis. His immune system started destroying his spinal cord. He was young, healthy, athletic, and had previously received tetanus shots without issue. He is now wheel chair bound, can barely move and is in intense pain 24/7. The injection caused every muscle in his body to spasm causing unbearable pain.
One big question about this for me is wondering if any group is looking for why this happened. I feel that either the pharmaceutical company or the government should be spending significant research dollars understanding what happened in this case.
It also shows that vaccines are not 100% safe, which seems to be the general narrative. When the truth maybe something more like you have a 1 in 10 million chance of living the rest of your life in agony, but you are required to accept the risk for the good of everyone.
So maybe collecting the blood markers suggested by the parent poster would be a step in understanding why things go so badly for some people.
One big question about this for me is wondering if any group is looking for why this happened. I feel that either the pharmaceutical company or the government should be spending significant research dollars understanding what happened in this case.
It also shows that vaccines are not 100% safe, which seems to be the general narrative. When the truth maybe something more like you have a 1 in 10 million chance of living the rest of your life in agony, but you are required to accept the risk for the good of everyone.
So maybe collecting the blood markers suggested by the parent poster would be a step in understanding why things go so badly for some people.
> (AstraZeneca using meningitis vaccine as control instead of true placebo).
AFAICR, this was done on purpose to prevent people from figuring out they got a vaccine shot, because an inert placebo wouldn't cause any side effects.
AFAICR, this was done on purpose to prevent people from figuring out they got a vaccine shot, because an inert placebo wouldn't cause any side effects.
A shot with saline would help demonstrate some of the side effects (localized aches or damage to the muscle), but would not elicit the same response as different vaccine with roughly known side effects (feedback on vaccine administration reactions is far from ideal). The other possibility is minimizing the appearance of side effects by comparing against the control group.
this is encouraging - hope the side effects at those lower doses don't turn out to be significant.
How does the Moderna mRNA vaccine differ from the other mRNA vaccine in Phase 1/2 trials - BioNTech/Pfizer?
How does the Moderna mRNA vaccine differ from the other mRNA vaccine in Phase 1/2 trials - BioNTech/Pfizer?
Derek Lowe's last blog post was about Pfizer/BioNTech. He discussed Pfizer's CEO comments and their Phase I data.
Lowe seems optimistic.
https://blogs.sciencemag.org/pipeline/archives/2020/07/14/pf...
nice. Looking forward to his Moderna results blog post.
Oxford/AstraZeneca paper being published tomorrow too in Lancet I think.
Fingers crossed one of these will pan out quick! Winter wave would be ruthless
Oxford/AstraZeneca paper being published tomorrow too in Lancet I think.
Fingers crossed one of these will pan out quick! Winter wave would be ruthless
Oh, good. Sooner than I thought for Chaddox.
Chaddox has its downsides, but I think it'll be an effective band aid solution. As far as mRNA vaccines, I read that blog post and think Lowe, (and other biologists) have more hope for Pfizer than they do for Moderna. However, Pfizer's vaccine needs more time.
Chaddox has its downsides, but I think it'll be an effective band aid solution. As far as mRNA vaccines, I read that blog post and think Lowe, (and other biologists) have more hope for Pfizer than they do for Moderna. However, Pfizer's vaccine needs more time.
Nice
I'm very nervous about the safety of any vaccine based on a complete spike protein, and worried that if one is rushed to market it will have such disastrous side effects that it will be an antivaxxer talking point for the next century.
The only vaccines I'm really excited about are the ones based on S1 Receptor Binding Domain (RBD), none of which are yet in stage 1.
The only vaccines I'm really excited about are the ones based on S1 Receptor Binding Domain (RBD), none of which are yet in stage 1.
I'm very nervous about the safety of any vaccine based on a complete spike protein
S1 Receptor Binding Domain (RBD), What make one more worrying than the other? I have not the expertise to make such inferences
S1 Receptor Binding Domain (RBD), What make one more worrying than the other? I have not the expertise to make such inferences
I'm guessing they have target specificity concerns. I'm no spike protein expert, but the concern would be that spike-targeting ligands can bind to other off-target sites, leading to unexpected and unwanted side effects.
What they think these side effects might be, I have no idea.
What they think these side effects might be, I have no idea.
Vs targeting receptors?
There are a few possibilities in my mind.
* T Cell mediated inflammatory cascade (Cytokine storm) caused by off-target cross-reactivity with IL-11: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092895/
* Autoimmune responses: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809466/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246018/
* Antibody-Dependent Enhancement of viral entry: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018502/
* T Cell mediated inflammatory cascade (Cytokine storm) caused by off-target cross-reactivity with IL-11: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092895/
* Autoimmune responses: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809466/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246018/
* Antibody-Dependent Enhancement of viral entry: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018502/
Very thoughtful point. I was concerned about it as well. Rushing a half-backed vaccine that has serious side-effects will fuel antivaxxers for decades.
Frankly I don't buy that.
There has actually been something like this during the swine flu pandemic. There was a vaccine that is believed to have caused some cases of narcolepsy. This was a real, bad sideeffect with a vaccine that was rushed to market.
Surprisingly this isn't a big talking point in antivaccine circles. Yeah you'll hear about it sometimes, but compare it to the number of times you hear "somethingsomething MMR aluminium autism" which is all debunked bullshit - you'll hear that far more often.
What I want to say is: Antivaccine people largely don't care about real issues with vaccines. They're happy with their pseudoscientific nonsense, that's good enough for them to reject every vaccine ever made.
There has actually been something like this during the swine flu pandemic. There was a vaccine that is believed to have caused some cases of narcolepsy. This was a real, bad sideeffect with a vaccine that was rushed to market.
Surprisingly this isn't a big talking point in antivaccine circles. Yeah you'll hear about it sometimes, but compare it to the number of times you hear "somethingsomething MMR aluminium autism" which is all debunked bullshit - you'll hear that far more often.
What I want to say is: Antivaccine people largely don't care about real issues with vaccines. They're happy with their pseudoscientific nonsense, that's good enough for them to reject every vaccine ever made.
I also happen to agree with you it is very unlikely that more people will become anti-vaxer just because covid vaccine was not effective.
Death of their kids has fueled them for centuries and they don't see that concerned about it.
How does this compare to the Oxford/AZ vaccine?
Taking relatively healthy aged population group and feeding them placebo could achieve similar outcome?
Phase 1 trials are primarily to demonstrate safety. Data about efficacy is a nice bonus, but a Phase 2 trial should be large enough to show more clearly whether it's effective.
But they already are testing their blood for effectiveness. I have to say, if a placebo can cause your blood cells to fight off a disease better even when removed from your body, that would be something.
A placebo is not necessary in this phase (phase 0). The most important thing is that the vaccine is safe and that there is a dose dependent relationship.
The placebo will only be necessary in later trial stages. Now it's mostly to assess safety and efficacy through immunological parameters.
Not much is known about the humans immunological response to covid or this vaccine. Derek Lowe is rightly pointing out that it's way too early to say if this is even effective against COVID. The safety and dose-dependency is just the first step in the process.
Not much is known about the humans immunological response to covid or this vaccine. Derek Lowe is rightly pointing out that it's way too early to say if this is even effective against COVID. The safety and dose-dependency is just the first step in the process.
No. This says the vaccine looks pretty good, and with effects we hope will prove better than placebo.
It's quite incredible. This chemical appears to have a safety profile comparable with the coronavirus itself, and yet the stock market appears to anticipate a possibility that people will get injected with it en masse.
That's because the one thing certainly Moderna has been good at is hype. Many biologists have been pretty skeptical about an mRNA vaccine and yet Moderna has been riding high.
1) No data for the most vulnerable older (>55) population
2) Second dose absolutely necessary
3) Safety profile less than desirable
4) Durability of neutralizing Ab not so encouraging (decline from day 43~57)
5) Very low CD8 T-cell responses
Novavas phase I results (NVX-CoV2373), probably due to be out soon, will be interesting.