16 ms·

Moderna’s SARS-CoV-2 Vaccine Phase I Data

158 points by hprotagonist 6y ago

pen2l 6y ago
Pasting from linked twitter thread, while this is encouraging, some things are left to be desired: 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.
- objektif 6y ago
  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.
  - SiempreViernes 6y ago
    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.
  - rollinggoron 6y ago
    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.
    - kgwgk 6y ago
      Not just side effects in this case.
  - claudeganon 6y ago
    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-twice-reinfection-antibody-herd-immunity https://www.vox.com/2020/7/12/21321653/getting-covid-19-twic...
    - kardos 6y ago
      So do we solve that with 4x a year vaccination?
      - greesil 6y ago
        At least until something better comes along.
        macintux 6y ago
        I'd be curious how long, and how much money would be required, to ramp up vaccine production to 20+ billion doses/year.
        loeg 6y ago
        Just spitballing here, but I'd expect it's several orders of magnitude cheaper than keeping the economy shut down for the same duration.
        tzs 6y ago
        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.
  - dicomdan 6y ago
    What you're saying about CanSino is purely false and smells of propaganda: https://www.fool.com/investing/2020/07/07/cansinos-covid-19-vaccine-was-just-approved-for-li.aspx https://www.fool.com/investing/2020/07/07/cansinos-covid-19-... It's not even a serious candidate due to lack of efficacy and actually dangerous side effects, so far.
    - dang 6y ago
      > 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 https://news.ycombinator.com/newsguidelines.html
  - snapetom 6y ago
    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.
- cactus2093 6y ago
  What's the issue with the safety profile?
  - tempsy 6y ago
    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?
    - mlyle 6y ago
      > 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.
    - loeg 6y ago
      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.
    - capkutay 6y ago
      They already eliminated the highest dose given the lower dose also produced significant antibodies.
      - koheripbal 6y ago
        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.
- dicomdan 6y ago
  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.
  - ProAm 6y ago
    > Stock market is reacting very positively to this vaccine. The stock market should be considered because of why?
    - ihattendorf 6y ago
      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.
      - ct520 6y ago
        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 .
      - hellofunk 6y ago
        If you honestly believe that, I certainly hope you’re not actively trading the market!
      - koheripbal 6y ago
        In many cases, that's correct - but not when the issue is emotional and outside the normal investor field of expertise.
      - klondike_klive 6y ago
        Because of your use of the words "some people" and "perfectly" I'm reading your comment as sarcasm.
- capkutay 6y ago
  > 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.
- fuzzythinker 6y ago
  INO-4800 phase I peer review results will be out soon.
rossdavidh 6y ago
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.
- The_rationalist 6y ago
  * 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.
  - sp332 6y ago
    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.
  - paxswill 6y ago
    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/challenge-testing https://blogs.sciencemag.org/pipeline/archives/2020/07/02/ch...
Trias11 6y ago
Taking relatively healthy aged population group and feeding them placebo could achieve similar outcome?
- sp332 6y ago
  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.
  - mxcrossb 6y ago
    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.
- mchusma 6y ago
  No. This says the vaccine looks pretty good, and with effects we hope will prove better than placebo.
- deugtniet 6y ago
  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.
The_rationalist 6y ago
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!
- thepangolino 6y ago
  The two injections are mostly due to safety protocols.
- christoph 6y ago
  On the linked Twitter thread from the article there is a link to the AE chart https://twitter.com/RNAiAnalyst/status/1283149377427701761/photo/1 https://twitter.com/RNAiAnalyst/status/1283149377427701761/p...
  - The_rationalist 6y ago
    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
    - searine 6y ago
      >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.
AprilArcus 6y ago
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.
- addictedcs 6y ago
  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.
  - hannob 6y ago
    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.
    - objektif 6y ago
      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.
  - WrtCdEvrydy 6y ago
    Death of their kids has fueled them for centuries and they don't see that concerned about it.
- The_rationalist 6y ago
melling 6y ago
“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?
- sp332 6y ago
  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.
  - bluGill 6y ago
    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.
    - OkGoDoIt 6y ago
      From the original article, it sounds like the first round is only minimally effective, and the major boost comes from the second round.
      - bluGill 6y ago
        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.
- creaghpatr 6y ago
  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.
dharma1 6y ago
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?
- snapetom 6y ago
  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/pfizers-progress https://blogs.sciencemag.org/pipeline/archives/2020/07/14/pf...
  - dharma1 6y ago
    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
    - snapetom 6y ago
      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.
chvid 6y ago
This NY Times overview of various candidate vaccines is interesting: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html https://www.nytimes.com/interactive/2020/science/coronavirus... Coronavirus Vaccine Tracker
- EarthIsHome 6y ago
  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.
  - chvid 6y ago
    It is approved only for use within the Chinese military.
    - lbeltrame 6y ago
      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.
      - sudosysgen 6y ago
        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/PIIS0140-6736(20)31208-3/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
mchusma 6y ago
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/ https://1daysooner.org/ - no affiliation although I volunteered).
- ljf 6y ago
  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.
  - quicklime 6y ago
    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?
    - ljf 6y ago
      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.
mathdev 6y ago
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.
- snapetom 6y ago
  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.
DrBazza 6y ago
The author of that article also writes these fascinating articles "Things I won't work with" https://blogs.sciencemag.org/pipeline/archives/category/things-i-wont-work-with https://blogs.sciencemag.org/pipeline/archives/category/thin...
- ethbro 6y ago
  Derek Lowe's base blog is better, and more active, currently: https://blogs.sciencemag.org/pipeline/ https://blogs.sciencemag.org/pipeline/
maxehmookau 6y ago
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 https://www.ovg.ox.ac.uk/news/covid-19-vaccine-development It's supposedly a "front-runner" but also who knows!
- ttul 6y ago
  How frequently do you get tested for the virus?
  - maxehmookau 6y ago
    Weekly with a PCR swab. 2-monthly for antibodies via a blood sample.
    - ttul 6y ago
      Ouch!
      - maxehmookau 6y ago
        It's not that bad. You get used to it pretty quickly!
- coding123 6y ago
  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?
  - maxehmookau 6y ago
    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 :)
lymeeducator 6y ago
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).
- wyattpeak 6y ago
  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.
  - lymeeducator 6y ago
    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.
    - jbob2000 6y ago
jakozaur 6y ago
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-vaccine-update-oxford.html https://www.nytimes.com/2020/04/27/world/europe/coronavirus-...
- woofie11 6y ago
  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.
  - shorts_theory 6y ago
    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.
    - woofie11 6y ago
      Thank you!
- rurp 6y ago
DrScientist 6y ago
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.
- guruz 6y ago
  For the record, other companies are having (early) success with RNA too. BioNTech https://investors.biontech.de/news-releases/news-release-details/pfizer-and-biontech-announce-early-positive-data-ongoing-phase/ https://investors.biontech.de/news-releases/news-release-det... CureVac https://www.curevac.com/news/curevac-s-optimized-mrna-platform-provides-positive-pre-clinical-results-at-low-dose-for-coronavirus-vaccine-candidate https://www.curevac.com/news/curevac-s-optimized-mrna-platfo...
niccolop 6y ago
How does this compare to the Oxford/AZ vaccine?
tayebhid 6y ago
Nice

158 points by hprotagonist 6y ago

Pasting from linked twitter thread, while this is encouraging, some things are left to be desired: 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.

objektif 6y ago
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.
- SiempreViernes 6y ago
  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.
- rollinggoron 6y ago
  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.
  - kgwgk 6y ago
    Not just side effects in this case.
- claudeganon 6y ago
  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-twice-reinfection-antibody-herd-immunity https://www.vox.com/2020/7/12/21321653/getting-covid-19-twic...
  - kardos 6y ago
    So do we solve that with 4x a year vaccination?
    - greesil 6y ago
      At least until something better comes along.
      - macintux 6y ago
        I'd be curious how long, and how much money would be required, to ramp up vaccine production to 20+ billion doses/year.
        loeg 6y ago
        Just spitballing here, but I'd expect it's several orders of magnitude cheaper than keeping the economy shut down for the same duration.
      - tzs 6y ago
        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.
- dicomdan 6y ago
  What you're saying about CanSino is purely false and smells of propaganda: https://www.fool.com/investing/2020/07/07/cansinos-covid-19-vaccine-was-just-approved-for-li.aspx https://www.fool.com/investing/2020/07/07/cansinos-covid-19-... It's not even a serious candidate due to lack of efficacy and actually dangerous side effects, so far.
  - dang 6y ago
    > 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 https://news.ycombinator.com/newsguidelines.html
- snapetom 6y ago
  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.
cactus2093 6y ago
What's the issue with the safety profile?
- tempsy 6y ago
  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?
  - mlyle 6y ago
    > 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.
  - loeg 6y ago
    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.
  - capkutay 6y ago
    They already eliminated the highest dose given the lower dose also produced significant antibodies.
    - koheripbal 6y ago
      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.
dicomdan 6y ago
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.
- ProAm 6y ago
  > Stock market is reacting very positively to this vaccine. The stock market should be considered because of why?
  - ihattendorf 6y ago
    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.
    - ct520 6y ago
      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 .
    - hellofunk 6y ago
      If you honestly believe that, I certainly hope you’re not actively trading the market!
    - koheripbal 6y ago
      In many cases, that's correct - but not when the issue is emotional and outside the normal investor field of expertise.
    - klondike_klive 6y ago
      Because of your use of the words "some people" and "perfectly" I'm reading your comment as sarcasm.
capkutay 6y ago
> 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.
fuzzythinker 6y ago
INO-4800 phase I peer review results will be out soon.

rossdavidh 6y ago

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.

The_rationalist 6y ago
* 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.
- sp332 6y ago
  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.
- paxswill 6y ago
  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/challenge-testing https://blogs.sciencemag.org/pipeline/archives/2020/07/02/ch...

Trias11 6y ago

Taking relatively healthy aged population group and feeding them placebo could achieve similar outcome?

sp332 6y ago
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.
- mxcrossb 6y ago
  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.
mchusma 6y ago
No. This says the vaccine looks pretty good, and with effects we hope will prove better than placebo.
deugtniet 6y ago
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.

The_rationalist 6y ago

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!

thepangolino 6y ago
The two injections are mostly due to safety protocols.
christoph 6y ago
On the linked Twitter thread from the article there is a link to the AE chart https://twitter.com/RNAiAnalyst/status/1283149377427701761/photo/1 https://twitter.com/RNAiAnalyst/status/1283149377427701761/p...
- The_rationalist 6y ago
  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
  - searine 6y ago
    >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.

AprilArcus 6y ago

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.

addictedcs 6y ago
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.
- hannob 6y ago
  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.
  - objektif 6y ago
    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.
- WrtCdEvrydy 6y ago
  Death of their kids has fueled them for centuries and they don't see that concerned about it.
The_rationalist 6y ago

melling 6y ago

“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?

sp332 6y ago
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.
- bluGill 6y ago
  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.
  - OkGoDoIt 6y ago
    From the original article, it sounds like the first round is only minimally effective, and the major boost comes from the second round.
    - bluGill 6y ago
      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.
creaghpatr 6y ago
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.

dharma1 6y ago

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?

snapetom 6y ago
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/pfizers-progress https://blogs.sciencemag.org/pipeline/archives/2020/07/14/pf...
- dharma1 6y ago
  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
  - snapetom 6y ago
    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.

chvid 6y ago

This NY Times overview of various candidate vaccines is interesting: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html https://www.nytimes.com/interactive/2020/science/coronavirus... Coronavirus Vaccine Tracker

EarthIsHome 6y ago
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.
- chvid 6y ago
  It is approved only for use within the Chinese military.
  - lbeltrame 6y ago
    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.
    - sudosysgen 6y ago
      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/PIIS0140-6736(20)31208-3/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

mchusma 6y ago

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/ https://1daysooner.org/ - no affiliation although I volunteered).

ljf 6y ago
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.
- quicklime 6y ago
  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?
  - ljf 6y ago
    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.

mathdev 6y ago

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.

snapetom 6y ago
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.

DrBazza 6y ago

The author of that article also writes these fascinating articles "Things I won't work with" https://blogs.sciencemag.org/pipeline/archives/category/things-i-wont-work-with https://blogs.sciencemag.org/pipeline/archives/category/thin...

ethbro 6y ago
Derek Lowe's base blog is better, and more active, currently: https://blogs.sciencemag.org/pipeline/ https://blogs.sciencemag.org/pipeline/

maxehmookau 6y ago

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 https://www.ovg.ox.ac.uk/news/covid-19-vaccine-development It's supposedly a "front-runner" but also who knows!

ttul 6y ago
How frequently do you get tested for the virus?
- maxehmookau 6y ago
  Weekly with a PCR swab. 2-monthly for antibodies via a blood sample.
  - ttul 6y ago
    Ouch!
    - maxehmookau 6y ago
      It's not that bad. You get used to it pretty quickly!
coding123 6y ago
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?
- maxehmookau 6y ago
  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 :)

lymeeducator 6y ago

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).

wyattpeak 6y ago
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.
- lymeeducator 6y ago
  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.
  - jbob2000 6y ago

jakozaur 6y ago

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-vaccine-update-oxford.html https://www.nytimes.com/2020/04/27/world/europe/coronavirus-...

woofie11 6y ago
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.
- shorts_theory 6y ago
  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.
  - woofie11 6y ago
    Thank you!
rurp 6y ago

DrScientist 6y ago

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.

guruz 6y ago
For the record, other companies are having (early) success with RNA too. BioNTech https://investors.biontech.de/news-releases/news-release-details/pfizer-and-biontech-announce-early-positive-data-ongoing-phase/ https://investors.biontech.de/news-releases/news-release-det... CureVac https://www.curevac.com/news/curevac-s-optimized-mrna-platform-provides-positive-pre-clinical-results-at-low-dose-for-coronavirus-vaccine-candidate https://www.curevac.com/news/curevac-s-optimized-mrna-platfo...

niccolop 6y ago

How does this compare to the Oxford/AZ vaccine?

tayebhid 6y ago

Nice