It seems like they tested for antibodies, but this article makes no mention of challenges to the real virus.
It's important to remember that vaccines for previous coronaviruses (SARS/MERS) had reports of generating anitbodies, but also causing immunopathic responses or immune enhancement syndrome:
It's really really to early to say yes or no, and the fact that the article tries to make a claim either way, is worrying. Vaccines for new families of viruses traditionally take years or decades to develop. We still don't have vaccines for retroviruses like HIV/Herpes (and it may not be possible due to the nature of those viruses).
I've had all my vaccinations; I'm not an anti-vaxer. But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing.
Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine. There are trials underway for inhaled steroids that look very promising, and there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.
Having a viable treatment option seems much more valuable and safer than vaccinations in this particular case.
You are misunderstanding the point of this study. This is a Phase 1 study designed to show that the vaccine itself doesn't directly make people sick and to measure their antibody responses via blood tests.
The on-going Phase 2/3 trials in the UK, South Africa and Brazil are designed to establish the efficacy of the vaccine under viral challenge. The idea is that you vaccinate a bunch of people (and an equally-sized control group) and wait around until a subset of them test positive for the virus. Then you unblind the groups and make sure that the people who got sick were in the control group. You also check for ADE (antibody dependent enhancement) to make sure the vaccine doesn't amplify the strength of the virus.
All your questions are valid, but this study doesn't claim to answer them. Those results are still forthcoming. Additionally, the risk of ADE is well understood and carefully considered in the design of these trials.
(Disclaimer - I'm a participant in the UK Phase 2/3 trial)
The OP was critiquing the media reporting on the study not the study itself so I think your suggestion that the OP misunderstood the point of the study is off base.
The OP did not claim that the study sought to answer the questions posed. The article does answer the question 'Is it safe?' with the word 'Yes' so I believe you are actually in agreement with the OP and the OP did understand that it is really early to say that, hence the critique.
It is slightly different than a regular Phase 1 study because there's a control arm. I suspect they want to use the data as a complement to the Phase 2/3 results in the unfortunate case the volounteers end up positive for the virus.
It's still good to see such questions being raised in the community, especially when someone knowledgeable on the matter (such as yourself) has an educated response.
> (Disclaimer - I'm a participant in the UK Phase 2/3 trial)
I have always thought those medical trials are conducted under an NDA against the patient, meaning you do not only not know what group you are in, you are not even allowed to tell you are being observed in such a study (to prevent accidental unblinding).
> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine. There are trials underway for inhaled steroids that look very promising, and there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.
I think your perception of the numbers are a little off here. In the UK, we were loosing 1100 people a day entirely through covid (https://coronavirus.data.gov.uk/) That was most from a few hot spots like london. (less than 10% of the population.) We were very close to overwhelming hospitals. when a hospital system is overwhelmed you get a very large spike in deaths, because stuff that's treatable isn't treated
without lockdown, those deaths would have grown exponentially. Something like 200-400k preventable deaths.
so, if we want to get out of lockdown, we need to have something to reduce the spread of the virus. One way is heard immunity (thats what the US is doing, and its not going very well) another is vaccine.
Now, given the UK example, if the vaccine causes 10 deaths, and 1000 severe reactions(ie hospitalised) thats still better than the 200k deaths and close to a million cases with complications
Deaths arn't the whole picture, its the people that recover with life altering injuries as well.
>Deaths of people who have had a positive test result
These are people who died who tested positive for the the virus not people who died as a result of having the virus. Not very useful numbers since the virus spreads in hospitals.
FWIW Greater London is approx 13% of the UK population, and the London metropolitan area is approx 21%. Intentional under and over counting of the size of London is pretty common depending on the interlocutor's agenda
> Now, given the UK example, if the vaccine causes 10 deaths, and 1000 severe reactions(ie hospitalised) thats still better than the 200k deaths and close to a million cases with complications
The anti vaccination optics, of a vaccine killing people, would be so bad the resulting vaccination resistance could lead to millions of deaths.
Yes, statistics maybe say that it would be a good deal now. But if you assume it fuels the antivac fire and decreases measles vaccination by 10% for the next 10 years, then we are looking at a death toll 10-100 times larger than COVID in the future, from that disease alone.
The WHO says there is only one worse thing than a bad pandemic, and that's a bad vaccine.
Because not everybody is exposed to the pandemic, but in principle everyone is exposed to the vaccine.
That doesn't counter your point, but we'll need up to phase 3, to have enough coverage to make sure your statistics hold.
But indeed, the risk seems to be balanced against 5 years waiting for any long term symptoms to show.
>We still don't have vaccines for retroviruses like HIV/Herpes
Good thing this isn't a retrovirus.
>But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing.
They started on this vaccine about 9 years ago, originally for the first SARS/MERS. They just gave it to 1,077 people and all 100% produced the desired effect, and the worst symptom reported was fatigue/headache that resolved on its own within 24 hours, or sooner if taken Tylenol/paracetamol. We're losing ~150,000 people worldwide EVERY MONTH to this virus, how many more months/deaths should we wait until we're sufficiently satisfied that it's safe?
That's a good start. But for example, how many of them were pregnant, and at what stages? I would guess none. That would be the most famous way to get this wrong.
I hope they are thinking hard about the optimal roll-out strategy, though. It should surely be faster than in normal times. It might well be that you should run very very large not-quite-trials as the first stage of general distribution, and watch their evidence in real-time.
I feel like your reply is a bit dismissive of a very real problem.
I don't understand anything about biology/vaccines or anything else relevant - but there have been several stories in history of medicine that was thought to have no side effect, that ended up being taken off the shelves because it was more dangerous than first thought.
If we're going to inject a few hundred million (if not a few billion) people with something, we need to be really really sure it won't harm then, and considering the fact that COVID has a mortality rate of 1%-ish, the vaccine has a huge burden of proof.
And more importantly to anything that I say as a non-expert - most experts on these issues seem to think you need at least ~10 months of human trials, if not more.
I'd just add that nearly 20% of participants experienced a fever of over 100F after the vaccine, and about half felt feverish. Though, like you say, these numbers were reduced for participants that took Tylenol.
>>We're losing ~150,000 people worldwide EVERY MONTH to this virus, how many more months/deaths should we wait until we're sufficiently satisfied that it's safe?
Before vaccinating 7 billion people with a vaccine done in a year we should think at least twice, Darwin Award in global scale and all. Let them vaccinate 80+ year olds or people with one foot already in the grave, but be very careful before doing it in a massive scale.
Are you aware that rushed vaccines for pandemics have caused serious side effects that were not discovered until too late? This is not a theoretical concern. A study of 1000 people for 2 months is not nearly enough to detect the kinds of issues that have occurred in the past, let alone novel issues.
We need to ensure that the vaccine is extraordinarily safe. "But it saves more people than it kills" is not an argument people accept, unfortunately. If this vaccine kills anyone, the antivax fallout could be worse in the long run than just letting the virus run its course.
> Vaccines for new families of viruses traditionally take years or decades to develop.
Traditionally many things used to take an awful lot longer than it does now (e.g. gene sequencing). Technology advances.
Also, this vaccine was based on an earlier one developed for MERS so they weren't starting from scratch.
> We still don't have vaccines for retroviruses like HIV/Herpes
That's completely irrelevant because they're very different viruses. Vaccination for a coronavirus should be a lot easier.
> But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing
It is undergoing extensive testing. Tens of thousands of people are currently being given the vaccine. The timeline is not really relevant; what counts is the testing that is carried out.
I'm sure the Oxford University team has given proper consideration to safety.
> Traditionally many things used to take an awful lot longer than it does now (e.g. gene sequencing). Technology advances.
This may be true with chips and gene sequencing, but is not true for vaccines. The waiting period for vaccines is mainly for safety and efficacy, not waiting on technology like the other two.
We may become more certain some vaccines are safer given intrinsic properties, but that probably won't result in any statistically noticeable difference because it's very hard to tell how a vaccine will behave without actually trying it as far as I understand it.
> That's completely irrelevant because they're very different viruses. Vaccination for a coronavirus should be a lot easier [than for retroviruses like HIV/Herpes].
Why is that? Uneducated guess: because of the rapid mutations of those viruses and the way they go dormant and hide?
I find it disturbing that a post like this gets downvoted. You've said nothing off-the-wall here. A downvote is not a rebuttal or an unceremonious verdict on the validity of your thoughts. Seriously not a fan of downvotes for this reason...just a blight on public discourse.
To get back on topic, I'd really like someone to explain in some way that makes sense to me (because I've heard none--maybe I'm just incorrigible, thought) how a mandatory vaccine is justifiable for a disease with an extremely high survival rate that elderly people who've already exceeded the average life expectancy are disproportionately at risk for.
You're only looking at the death rate. Take a look at the hospitalization rate (~20% for all age groups) and the amount of resources it takes to just keep one person alive. ICUs and hospital staffs are stretched to the brink. People indeed are surviving, but at great expense, and the hospitals have said they can't keep this up much longer. In Houston, TX there was a doctor who had worked 117 days straight and had to be relieved by Army Medical personnel (https://abc13.com/health/85-soldiers-arriving-to-help-treat-...). There's just not enough ICU beds and medical staff to go around. Once we run out of hospital resources, the death rate will jump 5-10x. If that happens, you're talking 20+ million deaths in the U.S., on pace with the 1918 pandemic if not worse. If you think the economy is bad now, wait til 20+ million people suddenly aren't shopping anymore.
Lastly, consider all of the people who have "recovered" but haven't really recovered, this includes the young 20-30 yr old crowds. There's hundreds of support groups now focused on post-corona-syndrome where people are 100+ days into the recovery but still have symptoms, including brain damage, neurological issues, strokes, kidney failures, shortness of breath, etc. It seems as if the older people are dying, and the younger patients are surviving, but with long-term damage.
> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine.
> there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.
That's the reason for the down-votes, and for once I think it's actually appropriate. The rest of the post was fine, but those are some wildly controversial - if not completely incorrect and reckless - assumptions to make. For one, it's too early to make definitive statements like these. As far as I know, public health experts have made it well known the risk factor is enormously high and so it's worth being proactive than reactive. Clearly there's an enormous amount of effort in getting an emergency vaccine out and I would think for good reason. Nobody on HN is qualified to make statements on this, especially if they're not actively studying this disease or they're not a public health expert.
Don't worry about early downvotes too much. It doesn't show grey based on percentage of downvotes, it shows grey when it goes below 1 point. So if one guy votes it down soon after it's commented, it goes grey. Others usually come along to correct it.
What does "extremely high survival rate" mean? Around 0.5% of people who get this virus die. For a highly transmissible virus, that's incredibly scary. It means that left unchecked, around a million people will die in the US alone. That's a massive public health issue. Requiring people to accept a safe vaccine is completely reasonable and proportionate.
> elderly people who've already exceeded the average life expectancy
Letting hundreds of thousands of people (in the US alone) with easily a decade left to live die of a preventable disease is not ethical. What you're writing sounds extremely callous.
> We still don't have vaccines for retroviruses like HIV/Herpes
HIV is so fundamentally different that it doesn't make sense to include it as a comparison here.
> there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.
The virus isn't just going to "burn out" anytime soon. 143k deaths in the US already, and we likely haven't even hit 10% of the population being infected yet.
Treatments will help pull the death rate downwards, but without a vaccine we're likely looking at multiple hundreds of thousands more deaths.
Coronaviruses are very different. We've rarely had any this deadly before. All vaccines are different; they're not one blanket thing. Smallpox vaccines are attenuated virus (a virus that has mutated to be benign in humans; in the case of Smallpox, the first vaccine by Jenner was injecting people with Horsepox).
Most Influenza vaccines are heat treated/inactivated virus.
In all cases, vaccines try to produce antibodies and force our immune systems to develop a memory for a virus we haven't actually been exposed to. As shown in the links above, this might not work at all for coronavirus.
To some extent, the actual interactions of vaccines, are somewhat opaque. This In A Nutshell video shows a very small part of the adaptive immune system, greatly simplified:
The more deadly a virus is, the faster it does burn out. It runs out of hosts to infect or everyone develops an immunity. SARS/MERS may have had lower outbreaks because of how much more dangerous they were.
If you graph fatalities on a logarithmic scale, you'll see we're already well past the inflection point in the US:
The cases are going up, but the fatalities are not, indicating there may be a lot of over-counting. Keep in mind people who test positive but die of a car wreck are counted as COVID19. All these people getting surgery after 3 months are required to get tested just for their surgery, and a positive antibody test counts as an active case, even if they're not sick or have the virus at all.
It's so bad in the UK they've stopped reporting fatality numbers due to issues with the data.
Some balance needs to be struck. In addition to the virus being harmful to health, the mitigation measures in place to reduce spread are highly disruptive to society.
I don't think we can wait until the risk is zero, after all the risk of allowing the virus to continue is far from zero. You talk about unknowns, we don't know the long-term impact of the disease either. Damage to the heart and lungs, oxygen deprivation of the brain, the impact extends beyond a boolean live or die.
I agree. There are so many variables whose interaction is influenced by each individual's unique immune expression, that we need to measure more of those variables for everyone to start identifying common patterns. I would hope that each vaccine volunteer has a minimum amount of testing (>= https://science.sciencemag.org/content/early/2020/07/15/scie...) before and after each vaccine dose. It would also be very beneficial to measure their HLA genetic SNPs (see GSK's MERS vaccine induced narcolepsy in 2009). Transparency and increased measurement of immune data will help improve and/or customize vaccines so that they are effective and safe.
The article actually _does_ mention challenges to the real virus, at the end of the "What are the next steps in the trial?" section:
> There are also calls to perform "challenge trials"[1] in which vaccinated people are deliberately infected with coronavirus. However, there are ethical concerns due to a lack of treatments.
> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine.
There might be a benefit in pushing it out to over 75s who are at severe risk from the virus (IFR 19%), or even over 65s (3%). Agree that it's not worth the risk of a barely understood vaccine on kids.
The article doesn't go into it, but the actual paper[1] states that this vaccine has "has previously been reported to be immunogenic and protective against pneumonia in a rhesus macaque challenge model", and cites to [2].
It's my understanding that phase 1 trials of this sort are designed simply to show that the potential vaccine generates a response in the recipient and doesn't causes any significant adverse effect. Phase 2 & 3 are where the the potential efficacy of the virus and the issues you raise are explored.
> Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine.
I strongly disagree with this sentiment. In the ideal world we would have both a treatment and a vaccine, but a vaccine is much preferable: even if it grants immunity for only a year it still allows for better logistics than a treatment. A treatment is also an unknown cost while the cost of producing a vaccine is fairly well know. Also there are loads of people who are at high risk and cannot survive COVID if they got it. Herd immunity and actual immunity from a vaccine is their only option for staying alive. Lastly, your comment makes it sound like steps are being skipped here. They are not. This vaccine along with others is undergoing the same three phase study approach as any other candidate for any other virus. The difference is that sometimes phase 1 and 2 are combined which puts the people in those trials at risk, but based on your comment I don’t see that as being one of your concerns (based on the part about how well yeah a lot of people died but it doesn’t warrant an emergency vaccine). It does not cause risk to anyone else and for successful phase 1 & 2 trials you can assume the vaccine is safe for the populations tested in phase 3. Once all three are cleared, the vaccine is just as safe as any other.
I know to a lot of people it may feel like corners are being cut but I have seen zero evidence for that. We are saving time by doing things like combining phase 1 & 2, expediting review and paperwork by prioritizing these candidates over other drugs, and in this particular case by manufacturing the vaccine while it’s still in trials, gambling that it will actually work. So far the Oxford vaccine looks to be the most promising of all so I would say it’s a good gamble, but then again only a small portion of that $1.2b is mine (coming from US tax dollars and AstraZenica coffers).
A true emergency vaccine is the only one that’s currently approved for use: it’s been approved as an experimental vaccine by the Chinese military for use by the military for one year. That particular vaccine doesn’t have phase 2 or 3 results actually published and the preliminary data from phase 2 doesn’t look as good as the Oxford one. That is the kind of thing I would personally hold off on, but not something that’s gone through all three phases and been independently reviewed.
Can some one please explain to me. Why are we focused on vaccine. Seems like vaccine is about 40% - 60% effective. With highly infectious disease is vaccine even effective? Would be good to hear from some one with a bit more medical knowledge
>It's really really to early to say yes or no, and the fact that the article tries to make a claim either way, is worrying.
This is exactly what the phase 1 trial (the result which were just released) tries to establish -
>Phase I trials were formerly referred to as “first-in-man studies” but the field generally moved to the gender-neutral language phrase "first-in-humans" in the 1990s;[5] these trials are the first stage of testing in human subjects.[6] They are designed to test the safety, side effects, best dose, and formulation method for the drug.[7] Phase I trials are not randomized, and thus are vulnerable to selection bias.[8]
It is good preliminary news. The real question if this vaccine prevents you spreading the disease or effectively turns you into an asymptomatic spreader. There also outstanding questions if this works well for elderly people, as vaccination are generally less effective if you are older. Basically news worth a small cheer, not an exuberant celebration quite yet.
The answer to your question is in the article. This is not an attenuated virus, nor is it variolation, it's a modified other virus (common cold) with some proteins added and does not cause an infection, it just stimulates antibodies.
It has been heavily modified, first so it cannot cause infections in people and also to make it "look" more like coronavirus.
Scientists did this by transferring the genetic instructions for the coronavirus's "spike protein" - the crucial tool it uses to invade our cells - to the vaccine they were developing.
The problem is not the vaccine, it is when you actual contract COVID-19 later on. If the vaccine sufficiently suppresses the symptoms, but doesn't actual prevent infection, there is a change you can spread the virus asymptomatically.
> It has been heavily modified, first so it cannot cause infections
Amusingly, lives would probably be saved if they had kept the base virus used for vaccination infectious. It's just the common cold, and the side effects are currently only a headache and fever, so getting the vaccination virus secondhand would be better than getting coronavirus, and you'd be protected after.
Even if it's made mandatory, which may not happen, manufacturing and distributing enough vaccines for everyone to get one will take years. Ideally we want to get everything back to normal once we have enough vaccines stocked up to strategically deploy in hot spots, but if the vaccine doesn't severely reduce the disease's spread that strategy won't be effective.
Logistically you can't give everyone the vaccine at the same time. If immunity is only temporary (few months) front line hospital staff are likely going to get vaccinated before the rest of society.
It would matter for those who can’t be vaccinated (the immuno compromised, very young children) or for those whom the vaccine might not be effective (very elderly with weak immune responses)
It would also matter for eradicating the virus. If it keeps circulating, and vaccines only provide protection for less than a lifetime, then we will have to keep vaccinating just about everyone in the world indefinitely. Any place that falls into civil strife could also expect a virus outbreak eventually.
It would still be great to have vaccine that merely made the virus without effect! But eradication would be better.
and also, how much time one people will be imune, and if new doses will be needed to reinforce the response of the imune system. People are saying September as a date for the vaccine to be avaliable, but it seens to be still many questions to answer before that.
Good, but the real question is whether the immune system will "remember" the vaccine for long enough. From [1]:
> Although the magnitude of neutralizing antibody (nAb) responses correlated with disease severity, there was a rapid decline in nAb titres in most patients within 3 months after onset of symptoms. [...] However, the consequences on secondary immune responses and their ability to prevent reinfection remain to be determined.
The immune system works that way that even single digit amount of antibodies can start a chain reaction very quickly.
I don't think it's possible to say a yes or no answer if somebody has immunity using a lab test today.
Though, the vaccine is only needed to last long enough to eradicate the virus. If mass application of vaccine can plunge the r-factor well below 1, it should be more than ok if its protection only lasts 3-4 months.
Hypothetically speaking if you were a front-line worker exposed to the public and the vaccine only worked reliably for 90 days wouldn't you get it quarterly? It seems like the prudent approach to get r0 well below until we can drain the reservoir of disease because as others have noted, getting enough vaccines deployed simultaneously globally could be a challenge.
If it's really down to a single company not being able to manufacture enough then it's time to open up the vaccine to licensing and let other companies pile in.
How long does it take to vaccinate the entire world?
If the each contaminated person transmits it to two other people, you'll need to keep half of the people immune to each at any single time. If you are doing this by vaccines, you'll need to give it to half of the people on that immunity window.
Interesting, I wonder if when we're developing the vaccine, ability to easily mass produce the vaccine is a factor... I imagine the biggest issue once we have a vaccine is going to be how to get it out to everyone quickly enough... like I can see critical care workers and then maybe elderly and it being this really long time before it can be available to everyone... or do you start mass production of the vaccine and avoid distribution until you have enough to get everyone vaccinated so that you have the protection period of 3-4 months? Interesting to think it's not just the science of the vaccine but also the application of the vaccine that can be a factor... In the meantime it's promising that we're also learning how to treat the infection better and better...
Not to belabor the point, but "r-factor" isn't the correct term here. If we're using a SIR model that assumes patients go from Susceptible (S) to Infected (I) and Recovered (R), we can still assume some proportion of patients can move back to the (S) compartment (i.e. losing immunity, what that is in reality for COVID obviously has a debate that I will not address here).
The "r-factor" (also called R_0, or attack rate), described the rate at which people once exposed to the virus move from S->I. The proportion of patients in (R) should not fundamentally change the r-factor.
That said, I do think your fundamental assessment in that moving more people from (S) directly to (R) would decrease the rate at which the disease spreads.
Given the USA's total failure at the presumably easier task of wide-scale testing, the notion that we could manufacture and distribute a novel vaccine in this time frame seems completely impossible. Maybe other countries could have success.
nAbs don't last forever, for any infectious virus. That's what T-Cells and B-Cells are for. This vaccine showed a T-Cell response, which means it SHOULD last long enough. T-Cells from SARS survivors have lasted 11+ years. But we won't know until 2-3 years from now. We can't wait that long. I say ship it to production now, and do a v2.0 release later.
This is a very dangerous approach and would just add fuel to the antivax fire. Even if drugs/vaccines are effective that does not mean that they do not come with severe side effects. Imagine injecting the whole population with Thalidomide...
But what exactly is long enough? Compared to repeated lockdowns, even monthly vaccine reinjections would be a relief because ramping production is easier than locking down. We don't really need perfect immunity, we just need to force average spread per infected to a value significantly lower than one and even a vaccine that turns out ineffective for a fraction of the population could be a major contributor to that. The most important concern is side effects, particularly antibody-dependent enhancement. Once production is the bottleneck things can only get better.
Considering we already do this once per year for the flu, its not even that unreasonable of a measure if its necessary to do monthly, bimonthly, quarterly, etc.
last thing you want is long term effects being harder than the disease itself. Even moderate effects will undermine trust in vaccines and the world absolutely can not afford that. I hope we’ll thread carefully here.
Making antibodies is a hugely expensive process in the body. You'd only want to do it for mortal dangers like Smallpox. So I'm pretty sure our body decides if it's worth it. The reason colds are endemic is that they aren't worth having a special forces team training to take them out of circulation at all times. You can just have the army look at it when there's an issue.
Do you have a source for this? I don't know much about immunology, but I know a little bit, and I don't think it's that thoughtful of a process. We have antibodies for all sorts of diseases, certainly not just for things like smallpox. This article suggests colds are endemic because they mutate too quickly for antibodies to be effective: https://www.technologynetworks.com/immunology/news/why-dont-... but we still make antibodies for them.
I'm curious why the share price slide after the mainstream news.
Sure, there have been rumours about the Lancet paper for a few days, maybe these were priced in already - and AstraZeneca has promised to manufacture it at cost or near cost. Still weird the market reacted this way
Outside of publicity, I don't see this as having an enormous impact on profits. Companies will be compelled to produce the vaccine in any event, and will be compensated, but I can't imagine governments would be purchasing the vaccine for any large markup.
I think it depends on the company, AstraZeneca CEO already said a while ago they will be manufacturing this at cost or near cost, this is a time for big pharma to give back. Some drug companies like Gilead though have very high markup, paid by the taxpayer.
And some bioteh companies with mRNA vaccines in phase 1/2 trials like Moderna and Biontech, or protein treatment like Synairgen have seen share prices skyrocket.
I guess the assumption is they will be collecting fees from the IP and/or future contracts for other drugs if this works out.
The problem is that this is a money-losing proposition. If ten companies attempt to produce a vaccine, spending X, and two of them succeed (before the rest), with the government paying each double their development costs (2X), that means that the expected outcome of developing a vaccine is -0.6X.
As a result, we should expect that most companies will only make a token effort.
That's unrealistically optimistic. The best case scenarios I've heard have it being deployed to healthcare workers late this year, and then hopefully be made available across the globe to approach the herd immunity threshold by the end of 2021, at least in some countries/communities. End of 2021 is an optimistic timeline to be talking about "major relief", and that's assuming no one messes with vaccine availability... Until then, we all need to take this extremely seriously and do everything we can to prevent spread.
Fauci has stated early 2021 as the goal for mass vaccination in the US if everything goes right. Provided that it works and provided that hundreds of millions of doses will be ready by EOY, and provided that the US govt. has already ordered enough of them - we can hope all the stars align. For the whole world, yes, it will take much longer than that.
>If all goes well, we should be looking at major relief by this year's end
While the news is encouraging, I think we need to pump the brakes a bit. It is very common for vaccine candidates to show promising cellular results (formation of neutralizing antibodies) and then utterly fall apart during actual efficacy testing (not actually prevent infection in people, or even actually make the infection worse when it happens). This is why most vaccines take 10-15 years to develop.
The paper (I'm sure it's been posted somewhere in thread). Surprisingly readable (if you have a basic understanding of immunology and Google), go check it out.
The TL;DR is they administered the vaccine to many people and compared the immune response, as measured by various immunology assays, and it elicited a noticeable response for every assay very close to the same responses from actual COVID patients. There were plenty of mild to moderate side effects, but they were reduced quite a bit using paracetamol (Tylenol, basically)
Readit News
It's important to remember that vaccines for previous coronaviruses (SARS/MERS) had reports of generating anitbodies, but also causing immunopathic responses or immune enhancement syndrome:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/
https://www.pnas.org/content/117/15/8218
>Is it safe?
It's really really to early to say yes or no, and the fact that the article tries to make a claim either way, is worrying. Vaccines for new families of viruses traditionally take years or decades to develop. We still don't have vaccines for retroviruses like HIV/Herpes (and it may not be possible due to the nature of those viruses).
I've had all my vaccinations; I'm not an anti-vaxer. But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing.
Although this virus has killed many, the risk factor for it is nowhere near high enough to warrant an emergency vaccine. There are trials underway for inhaled steroids that look very promising, and there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.
Having a viable treatment option seems much more valuable and safer than vaccinations in this particular case.
The on-going Phase 2/3 trials in the UK, South Africa and Brazil are designed to establish the efficacy of the vaccine under viral challenge. The idea is that you vaccinate a bunch of people (and an equally-sized control group) and wait around until a subset of them test positive for the virus. Then you unblind the groups and make sure that the people who got sick were in the control group. You also check for ADE (antibody dependent enhancement) to make sure the vaccine doesn't amplify the strength of the virus.
All your questions are valid, but this study doesn't claim to answer them. Those results are still forthcoming. Additionally, the risk of ADE is well understood and carefully considered in the design of these trials.
(Disclaimer - I'm a participant in the UK Phase 2/3 trial)
The OP did not claim that the study sought to answer the questions posed. The article does answer the question 'Is it safe?' with the word 'Yes' so I believe you are actually in agreement with the OP and the OP did understand that it is really early to say that, hence the critique.
I have always thought those medical trials are conducted under an NDA against the patient, meaning you do not only not know what group you are in, you are not even allowed to tell you are being observed in such a study (to prevent accidental unblinding).
I think your perception of the numbers are a little off here. In the UK, we were loosing 1100 people a day entirely through covid (https://coronavirus.data.gov.uk/) That was most from a few hot spots like london. (less than 10% of the population.) We were very close to overwhelming hospitals. when a hospital system is overwhelmed you get a very large spike in deaths, because stuff that's treatable isn't treated
without lockdown, those deaths would have grown exponentially. Something like 200-400k preventable deaths.
so, if we want to get out of lockdown, we need to have something to reduce the spread of the virus. One way is heard immunity (thats what the US is doing, and its not going very well) another is vaccine.
Now, given the UK example, if the vaccine causes 10 deaths, and 1000 severe reactions(ie hospitalised) thats still better than the 200k deaths and close to a million cases with complications
Deaths arn't the whole picture, its the people that recover with life altering injuries as well.
>COVID-19 associated UK deaths
>Deaths of people who have had a positive test result
These are people who died who tested positive for the the virus not people who died as a result of having the virus. Not very useful numbers since the virus spreads in hospitals.
The anti vaccination optics, of a vaccine killing people, would be so bad the resulting vaccination resistance could lead to millions of deaths.
Yes, statistics maybe say that it would be a good deal now. But if you assume it fuels the antivac fire and decreases measles vaccination by 10% for the next 10 years, then we are looking at a death toll 10-100 times larger than COVID in the future, from that disease alone.
That doesn't counter your point, but we'll need up to phase 3, to have enough coverage to make sure your statistics hold. But indeed, the risk seems to be balanced against 5 years waiting for any long term symptoms to show.
Without a vaccine - wouldn't herd immunity just be letting the virus spread and then let Darwin take over, more or less?
Good thing this isn't a retrovirus.
>But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing.
They started on this vaccine about 9 years ago, originally for the first SARS/MERS. They just gave it to 1,077 people and all 100% produced the desired effect, and the worst symptom reported was fatigue/headache that resolved on its own within 24 hours, or sooner if taken Tylenol/paracetamol. We're losing ~150,000 people worldwide EVERY MONTH to this virus, how many more months/deaths should we wait until we're sufficiently satisfied that it's safe?
That's a good start. But for example, how many of them were pregnant, and at what stages? I would guess none. That would be the most famous way to get this wrong.
I hope they are thinking hard about the optimal roll-out strategy, though. It should surely be faster than in normal times. It might well be that you should run very very large not-quite-trials as the first stage of general distribution, and watch their evidence in real-time.
I don't understand anything about biology/vaccines or anything else relevant - but there have been several stories in history of medicine that was thought to have no side effect, that ended up being taken off the shelves because it was more dangerous than first thought.
If we're going to inject a few hundred million (if not a few billion) people with something, we need to be really really sure it won't harm then, and considering the fact that COVID has a mortality rate of 1%-ish, the vaccine has a huge burden of proof.
And more importantly to anything that I say as a non-expert - most experts on these issues seem to think you need at least ~10 months of human trials, if not more.
Before vaccinating 7 billion people with a vaccine done in a year we should think at least twice, Darwin Award in global scale and all. Let them vaccinate 80+ year olds or people with one foot already in the grave, but be very careful before doing it in a massive scale.
We need to ensure that the vaccine is extraordinarily safe. "But it saves more people than it kills" is not an argument people accept, unfortunately. If this vaccine kills anyone, the antivax fallout could be worse in the long run than just letting the virus run its course.
For context: That is 0.0002% of the world's population.
Traditionally many things used to take an awful lot longer than it does now (e.g. gene sequencing). Technology advances.
Also, this vaccine was based on an earlier one developed for MERS so they weren't starting from scratch.
> We still don't have vaccines for retroviruses like HIV/Herpes
That's completely irrelevant because they're very different viruses. Vaccination for a coronavirus should be a lot easier.
> But I do have concerns on trying to push out any novel vaccine in less than two years without adequate testing
It is undergoing extensive testing. Tens of thousands of people are currently being given the vaccine. The timeline is not really relevant; what counts is the testing that is carried out.
I'm sure the Oxford University team has given proper consideration to safety.
This may be true with chips and gene sequencing, but is not true for vaccines. The waiting period for vaccines is mainly for safety and efficacy, not waiting on technology like the other two.
We may become more certain some vaccines are safer given intrinsic properties, but that probably won't result in any statistically noticeable difference because it's very hard to tell how a vaccine will behave without actually trying it as far as I understand it.
Why is that? Uneducated guess: because of the rapid mutations of those viruses and the way they go dormant and hide?
To get back on topic, I'd really like someone to explain in some way that makes sense to me (because I've heard none--maybe I'm just incorrigible, thought) how a mandatory vaccine is justifiable for a disease with an extremely high survival rate that elderly people who've already exceeded the average life expectancy are disproportionately at risk for.
Lastly, consider all of the people who have "recovered" but haven't really recovered, this includes the young 20-30 yr old crowds. There's hundreds of support groups now focused on post-corona-syndrome where people are 100+ days into the recovery but still have symptoms, including brain damage, neurological issues, strokes, kidney failures, shortness of breath, etc. It seems as if the older people are dying, and the younger patients are surviving, but with long-term damage.
> there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.
That's the reason for the down-votes, and for once I think it's actually appropriate. The rest of the post was fine, but those are some wildly controversial - if not completely incorrect and reckless - assumptions to make. For one, it's too early to make definitive statements like these. As far as I know, public health experts have made it well known the risk factor is enormously high and so it's worth being proactive than reactive. Clearly there's an enormous amount of effort in getting an emergency vaccine out and I would think for good reason. Nobody on HN is qualified to make statements on this, especially if they're not actively studying this disease or they're not a public health expert.
Where did the "mandatory" come from?
If a vaccine is promising but unproven, the sensible thing is to make it available to those who want to take the risk.
I agree that for a mandatory vaccine, you want a high level of certainty.
> elderly people who've already exceeded the average life expectancy
Letting hundreds of thousands of people (in the US alone) with easily a decade left to live die of a preventable disease is not ethical. What you're writing sounds extremely callous.
HIV is so fundamentally different that it doesn't make sense to include it as a comparison here.
> there's a good chance this virus will burn out in our population long before a truly safe vaccine comes to market.
The virus isn't just going to "burn out" anytime soon. 143k deaths in the US already, and we likely haven't even hit 10% of the population being infected yet.
Treatments will help pull the death rate downwards, but without a vaccine we're likely looking at multiple hundreds of thousands more deaths.
Coronaviruses are very different. We've rarely had any this deadly before. All vaccines are different; they're not one blanket thing. Smallpox vaccines are attenuated virus (a virus that has mutated to be benign in humans; in the case of Smallpox, the first vaccine by Jenner was injecting people with Horsepox).
Most Influenza vaccines are heat treated/inactivated virus.
In all cases, vaccines try to produce antibodies and force our immune systems to develop a memory for a virus we haven't actually been exposed to. As shown in the links above, this might not work at all for coronavirus.
To some extent, the actual interactions of vaccines, are somewhat opaque. This In A Nutshell video shows a very small part of the adaptive immune system, greatly simplified:
https://www.youtube.com/watch?v=BSypUV6QUNw
> The virus isn't just going to "burn out" anytime soon
Exponential growth doesn't go on forever. It has to hit an inflection point:
https://www.youtube.com/watch?v=Kas0tIxDvrg
The more deadly a virus is, the faster it does burn out. It runs out of hosts to infect or everyone develops an immunity. SARS/MERS may have had lower outbreaks because of how much more dangerous they were.
If you graph fatalities on a logarithmic scale, you'll see we're already well past the inflection point in the US:
https://aatishb.com/covidtrends/?data=deaths
The cases are going up, but the fatalities are not, indicating there may be a lot of over-counting. Keep in mind people who test positive but die of a car wreck are counted as COVID19. All these people getting surgery after 3 months are required to get tested just for their surgery, and a positive antibody test counts as an active case, even if they're not sick or have the virus at all.
It's so bad in the UK they've stopped reporting fatality numbers due to issues with the data.
I don't think we can wait until the risk is zero, after all the risk of allowing the virus to continue is far from zero. You talk about unknowns, we don't know the long-term impact of the disease either. Damage to the heart and lungs, oxygen deprivation of the brain, the impact extends beyond a boolean live or die.
> There are also calls to perform "challenge trials"[1] in which vaccinated people are deliberately infected with coronavirus. However, there are ethical concerns due to a lack of treatments.
[1] https://www.bbc.com/news/health-53426367
There might be a benefit in pushing it out to over 75s who are at severe risk from the virus (IFR 19%), or even over 65s (3%). Agree that it's not worth the risk of a barely understood vaccine on kids.
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[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
[2] https://www.biorxiv.org/content/10.1101/2020.05.13.093195v1
Herpes is not retrovirus. It just have a latent phase where inactive viral DNA is in the cytoplasm of infected neurons.
This sounds like how you get zombies. I’ve seen this movie before.
I strongly disagree with this sentiment. In the ideal world we would have both a treatment and a vaccine, but a vaccine is much preferable: even if it grants immunity for only a year it still allows for better logistics than a treatment. A treatment is also an unknown cost while the cost of producing a vaccine is fairly well know. Also there are loads of people who are at high risk and cannot survive COVID if they got it. Herd immunity and actual immunity from a vaccine is their only option for staying alive. Lastly, your comment makes it sound like steps are being skipped here. They are not. This vaccine along with others is undergoing the same three phase study approach as any other candidate for any other virus. The difference is that sometimes phase 1 and 2 are combined which puts the people in those trials at risk, but based on your comment I don’t see that as being one of your concerns (based on the part about how well yeah a lot of people died but it doesn’t warrant an emergency vaccine). It does not cause risk to anyone else and for successful phase 1 & 2 trials you can assume the vaccine is safe for the populations tested in phase 3. Once all three are cleared, the vaccine is just as safe as any other.
I know to a lot of people it may feel like corners are being cut but I have seen zero evidence for that. We are saving time by doing things like combining phase 1 & 2, expediting review and paperwork by prioritizing these candidates over other drugs, and in this particular case by manufacturing the vaccine while it’s still in trials, gambling that it will actually work. So far the Oxford vaccine looks to be the most promising of all so I would say it’s a good gamble, but then again only a small portion of that $1.2b is mine (coming from US tax dollars and AstraZenica coffers).
A true emergency vaccine is the only one that’s currently approved for use: it’s been approved as an experimental vaccine by the Chinese military for use by the military for one year. That particular vaccine doesn’t have phase 2 or 3 results actually published and the preliminary data from phase 2 doesn’t look as good as the Oxford one. That is the kind of thing I would personally hold off on, but not something that’s gone through all three phases and been independently reviewed.
For me, the things being developed are not 'vaccines' but are a different thing entirely with a similar intended purpose.
>It's really really to early to say yes or no, and the fact that the article tries to make a claim either way, is worrying.
This is exactly what the phase 1 trial (the result which were just released) tries to establish -
>Phase I trials were formerly referred to as “first-in-man studies” but the field generally moved to the gender-neutral language phrase "first-in-humans" in the 1990s;[5] these trials are the first stage of testing in human subjects.[6] They are designed to test the safety, side effects, best dose, and formulation method for the drug.[7] Phase I trials are not randomized, and thus are vulnerable to selection bias.[8]
https://en.m.wikipedia.org/wiki/Phases_of_clinical_research
https://marlin-prod.literatumonline.com/pb-assets/Lancet/pdf...
If I didn't have the context of 2020 and this article, I would swear that was an auto-generated random password.
Seems pretty well-named.
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It has been heavily modified, first so it cannot cause infections in people and also to make it "look" more like coronavirus. Scientists did this by transferring the genetic instructions for the coronavirus's "spike protein" - the crucial tool it uses to invade our cells - to the vaccine they were developing.
Amusingly, lives would probably be saved if they had kept the base virus used for vaccination infectious. It's just the common cold, and the side effects are currently only a headache and fever, so getting the vaccination virus secondhand would be better than getting coronavirus, and you'd be protected after.
It would also matter for eradicating the virus. If it keeps circulating, and vaccines only provide protection for less than a lifetime, then we will have to keep vaccinating just about everyone in the world indefinitely. Any place that falls into civil strife could also expect a virus outbreak eventually.
It would still be great to have vaccine that merely made the virus without effect! But eradication would be better.
> Although the magnitude of neutralizing antibody (nAb) responses correlated with disease severity, there was a rapid decline in nAb titres in most patients within 3 months after onset of symptoms. [...] However, the consequences on secondary immune responses and their ability to prevent reinfection remain to be determined.
[1]: https://www.nature.com/articles/s41577-020-0405-3
I don't think it's possible to say a yes or no answer if somebody has immunity using a lab test today.
Though, the vaccine is only needed to last long enough to eradicate the virus. If mass application of vaccine can plunge the r-factor well below 1, it should be more than ok if its protection only lasts 3-4 months.
If it's really down to a single company not being able to manufacture enough then it's time to open up the vaccine to licensing and let other companies pile in.
If the each contaminated person transmits it to two other people, you'll need to keep half of the people immune to each at any single time. If you are doing this by vaccines, you'll need to give it to half of the people on that immunity window.
And you must also syncronize it internationally.
Is anyone optimistic about that?
The "r-factor" (also called R_0, or attack rate), described the rate at which people once exposed to the virus move from S->I. The proportion of patients in (R) should not fundamentally change the r-factor.
That said, I do think your fundamental assessment in that moving more people from (S) directly to (R) would decrease the rate at which the disease spreads.
https://en.wikipedia.org/wiki/Compartmental_models_in_epidem...
https://www.nature.com/articles/s41586-020-2550-z
If this turns out to work in the short run, we should deploy it. Not wait 2 years while the pandemic rages to produce the perfect science paper.
We said that before, and we got Pandemrix.
Vaccination is safe. It's important we get as many people vaccinated as possible, and one of the ways we do that is by maintaining the safety.
https://en.wikipedia.org/wiki/Pandemrix
https://www.narcolepsy.org.uk/resources/pandemrix-narcolepsy
https://www.cdc.gov/vaccinesafety/concerns/history/narcoleps...
Sure, there have been rumours about the Lancet paper for a few days, maybe these were priced in already - and AstraZeneca has promised to manufacture it at cost or near cost. Still weird the market reacted this way
https://markets.businessinsider.com/news/stocks/astrazeneca-...
https://www.ig.com/en/trading-strategies/-buy-the-rumour--se...
And some bioteh companies with mRNA vaccines in phase 1/2 trials like Moderna and Biontech, or protein treatment like Synairgen have seen share prices skyrocket.
I guess the assumption is they will be collecting fees from the IP and/or future contracts for other drugs if this works out.
As a result, we should expect that most companies will only make a token effort.
If all goes well, we should be looking at major relief by this year's end.
https://www.reuters.com/article/us-health-coronavirus-oxford...
While the news is encouraging, I think we need to pump the brakes a bit. It is very common for vaccine candidates to show promising cellular results (formation of neutralizing antibodies) and then utterly fall apart during actual efficacy testing (not actually prevent infection in people, or even actually make the infection worse when it happens). This is why most vaccines take 10-15 years to develop.
The paper (I'm sure it's been posted somewhere in thread). Surprisingly readable (if you have a basic understanding of immunology and Google), go check it out.
The TL;DR is they administered the vaccine to many people and compared the immune response, as measured by various immunology assays, and it elicited a noticeable response for every assay very close to the same responses from actual COVID patients. There were plenty of mild to moderate side effects, but they were reduced quite a bit using paracetamol (Tylenol, basically)