Oxford University breakthrough on global COVID-19 vaccine

https://www.ox.ac.uk/news/2020-11-23-oxford-university-breakthrough-global-covid-19-vaccine

by mychaelangelo • 6 years ago

595 402 6 years ago

ox.ac.uk

bigpumpkin• 6 years ago

"These preliminary data indicate that the vaccine is 70.4% effective, with tests on two different dose regimens showing that the vaccine was 90% effective if administered at a half dose and then at a full dose, or 62% effective if administered in two full doses."

skrebbel• 6 years ago

Does anyone here who understands vaccines know how starting with a smaller does can improve effectiveness? It goes against my intuition.

BillyTheKing• 6 years ago

I wonder what the statistical significance is of those findings. I seems to me that they tried out various different approaches, so the sub-group that received this first-low-second-high treatment might be considerably smaller than the other groups combined leading to slightly less certainty in regards to the findings.

wbl3• 6 years ago

This vaccine is a viral vector vaccine. Immunity against the vector can be an issue, but this is moderately informed speculation.

evandijk70• 6 years ago

Isn't it more common to determine the dosing regime in Phase I/II trials, and use the Phase III trial as the final test for efficacy?

garmaine2• 6 years ago

Phase I/II establishes what a safe dose is. Phase III is when you get the first efficacy data.

bluGill7• 6 years ago

It is somewhat common to not be sure what is best after phase I/II and so try two different doses. Though normally you try to avoid that because it is more expensive. In this case Oxford thought the two dose was more promising, but the other had enough promise that they start it too just in case. That the second seems better is a surprise, if they expected this result they would have tested differently.

My guess is the lighter dose is really slightly less effective, but the same size is so small that statistical issues make it seem better than it really is.

mcdowall• 6 years ago

The key differentiator here is the storage requirements (2-8c ‘normal refrigerator’).

That’s much more accessible to developing / low GDP countries as opposed the cumbersome and expensive storage requirements of the other two.

wereHamster• 6 years ago

What are the storage requirements for the other two?

dragontamer3• 6 years ago

-80C for Pfizer, and below 0 for the other one (I forget exactly).

-80C is really close to dry-ice temperatures. So I wonder if its actually -80C or if the researchers were just saying "Dry Ice".

singingfish5• 6 years ago

-20c and -70c from what I remember

pvsukale3• 6 years ago

-80ºC for Pfizer vaccine and -20ºC for mRNA vaccine. https://www.npr.org/sections/health-shots/2020/11/17/9355633...

throwawayiionqz• 6 years ago

Another huge differentiator is price. At $3 to $4, many countries will jump on board ASAP and stay away from the expensive vaccines from Pfizer and Moderna.

bawolff12• 6 years ago

Maybe for less developed countries, but i think for major economies, the price difference is insignificant relative to the benefits of any vaccine.

ddeck• 6 years ago

At $3 to $4, many countries will jump on board ASAP and stay away from the expensive vaccines from Pfizer and Moderna.

The price difference will likely remain substantial, but in case anyone is unaware, the difference is currently greater due to AstraZeneca pledging to the sell the vaccine at cost "during the pandemic", while Pfizer and Moderna have indicated that they fully intend to profit. [1]

Once AstraZeneca deem the pandemic to be over, the price will likely rise.

It was reported a few months ago that internal AstraZeneca documents showed them projecting the "Pandemic Period" to end on 1 July 2021. [2]

[1] https://www.nytimes.com/2020/07/21/health/covid-19-vaccine-c...

[2] https://thehill.com/policy/healthcare/520202-astrazenecas-no...

guilamu• 6 years ago

Would you mind to add a source for those price estimates? Thanks!

Edit: just found a source here confirming what you said: https://www.bbc.com/news/health-55040635

onetimemanytime2• 6 years ago

Price is not an issue for rich countries. 500 Million vaccines for USA leaving kids and some other out...cost, what $25 Billion? Peanuts, compared to the damage it did /can do. Same for USA, EU, Japan, CA, Australia etc.

noneeeed• 6 years ago

Yeah, the fact that this doesn't even need a freezer is great news.

The fact that we have three highly effective vaccines in such a short period is amazing and between them we might stand a chance of making and distributing them at the scale necessary to get things under some kind of control by August.

beagle310• 6 years ago

The safety concerns cannot be resolved yet. Effective - yes. Safe? We won’t know for a while.

Pandemrix, a flu vaccine, caused a notable uptick in narcolepsy in Sweden, Finland and likely the UK. This was not (and could not) be seen in smaller trial populations.

It is not a given that any of the covid vaccines is safe enough. Historically, two cases of rushed vaccines (cutter polio and Gullah barre) were worse than the disease - and these were for diseases worse than covid. Those were 50-60 years ago. Pandemrix was 10-20. I’m not sure we’re that much better on safety now to rush vaccines.

jjeaff• 6 years ago

I think the cold storage issues are a bit overblown.

Apparently the pfizer and Moderna vaccines will keep for 30 days at refrigerator temps after thawing out. You can ship in dry ice and then I can't imagine the vaccine sitting around in any doctors office or pharmacy for longer than 30 days.

kul_• 6 years ago

Moderna vaccine also seems to have similar storage requirements with a high price tag. BioNTech otoh has impractical storage requirements for the third world. AstraZenca's price and storage combiation may open possibilities for distributing this globally.

nbevans• 6 years ago

I'd argue that it is more accessible to everyone including developed nations. It only requires a standard technology freezer - like that you have in a residential home. COVID-19 has already cost the UK hundreds of billions, so being able to roll out a vaccine with minimum hassle and without needing specialist storage and training on its handling, is an absolutely enormous benefit.

Honestly I feel like this vaccine is going to leave the mRNA-based vaccines trailing in its wake in terms of global government adoption.

Ciantic• 6 years ago

Moderna's vaccine can be stored in normal refrigerator (at 2 to 8 degrees Celsius) for 30 days. It also can be freezed for longer storage. [1]

However for developing world the prices becomes the issue, so you are probably right, this vaccine is cheaper and thus more available.

[1] https://www.nationalgeographic.com/science/2020/11/moderna-e...

Demiurge• 6 years ago

Also worth mentioning, is that Russia is working on a freeze dried version: https://www.nasdaq.com/articles/exclusive-russia-focuses-on-...

gumby3• 6 years ago

The key differentiator is the mechanism of action, not the storage system.

The other two current candidates are mRNA vaccines, an approach which hasn't been used in humans before -- looks like the harbinger of a revolution but we have no past experience.

This O/AZ uses the actual spike protein embedded in a simian virus (that does not affect humans and has its own DNA removed). It's possible to generate antibodies to the vehicle (virus) which is why a simian virus is used (humans won't already have encountered it) but also means your own immune system could target the vaccine itself. Loewe speculates that this is why the higher dose was less effective.

jeromegv• 6 years ago

The storage system is important and a key differentiator, tons of countries cannot effectively distribute a virus at -70° to population in the most vulnerable spots. I don't know why you felt the need to be so dismissive.

stingraycharles• 6 years ago

What does this imply? Is the approach by Oxford worse, or just more well known / less surprises? Does this mean that dosing the vaccination is somehow more difficult?

Sorry I’m a total noob in this area.

toshk3• 6 years ago

The press release is interesting. Not the best way to present their data. Immediate conclusion of many newspapers is "oxford vaccine is less effective then...".

dageshi3• 6 years ago

Better that than to be seen to overstate its effectiveness. The worst case scenario is people refuse to take it because they think they're being lied too or manipulated in some way.

toshk3• 6 years ago

Maybe. But it's also time to compete and current headlines are not working. If the public opinion is that it's far less effective then the other 2, what is happening now, you are putting the politicians in a difficult position that want to buy your vaccine. If you dig deeper you will find results for all vaccins are pretty similar. For instance even though one of the trials with Oxford vaccine had more people with Covid sypmtoms they had no severe cases, compared to one severe case with the Pfizer trial. And the total for both are too low to make definite conclusions.

tokamak-teapot• 6 years ago

On the (BBC) radio news earlier only the 90% figure was mentioned, not the 70%. This differs from the BBC news website, which started with the 70% figure and mentioned the 90% afterwards.

2Gkashmiri• 6 years ago

over 7 billion human population, a 90% effectiveness is what? alright? please enlighten me. does anyone know what was the effectiveness of the smallpox vaccine that we did actually manage to eradicate successfully?

ilogik• 6 years ago

this is different for each disease based on how quickly it transmits.

for SARS-COV-2 you need around 70% immunity in the population to achieve herd immunity

kuu2• 6 years ago

you need around 70% immunity in the population

This is the required immunity of the population, but not the effectiveness of the vaccine. Inside the population there are groups that you cannot put the vaccine (smallest babies, immunosuppressed people, etc).

howlgarnish3• 6 years ago

Dr Fauci stated earlier that he was hoping for 70% efficacy. So these results are still good, not just as good as the 94% seen earlier for Moderna's vaccine.

Tomminn• 6 years ago

The key point is that if you lower the replication rate-- the number of people each person with the virus goes on to infect-- below 1, the number of active cases exponentially decays to zero.

The business-as-usual replication rate of covid appears to be somewhere around 4-6, meaning that if we have universal vaccination with something like 80% efficacy, the number of active cases will exponentially decay with no other measures taken (social distancing, masks, lockdowns, quarantines etc).

_Microft3• 6 years ago

The disease will 'die out' (in quotes because it will not actually) if there are not enough targets that are susceptible to it.

People infected by SARS-Cov2 seem to infect two to six other people [0]. Reduce this number by 90% and we are well below one infection per infected, so it is not sustained. This assumes that everyone would be vaccinated.

Currently we are doing something similar: each measure like wearing a mask, social distancing, meeting fewer people, ventilating rooms, finding infected people before they can infect someone else ("contact tracing") contributes to reducing the number of follow-up infections a bit. (This is why "but masks do not really work" is an ill-informed argument. They do not have to because they are meant to be used together with other measures to achieve reduction in spread)

A vaccine will protect us passively instead of requiring us to actively following these measures and will therefore be a lot more convenient.

[0] https://en.wikipedia.org/wiki/Basic_reproduction_number

jaclaz• 6 years ago

Yes.

In case of need, the Swiss cheese model:

https://mobile.twitter.com/sketchplanator/status/13127289416...

unlikelymordant• 6 years ago

This depends on the r0 of the virus, an r0 of 2 means a 50% effective vaccine (and 100% vaccinated pop) will defeat the virus. With measles and a r0 of 18, youd need an effectiveness of 95%. Considering not everyone can or will take a vaccine, the effectiveness needs to be higher than this.

Covid is apparently around 3, and if you can vaccinate 90% of the population then an effectiveness of 75% would be the minimum you could get away with.

jbb67• 6 years ago

This is if everyone is equally likely to spread the virus.

Probably 20% of people are responsible for 80% of infections. (People who work in shops or public places, people in large extended families, people who socialize a lot).

If you can identify and vaccinate those people it will be much more that 20% effective. (It might be hard to identify those but it's probably easy to identify people at low risk of spreading it and infer)

bawolff12• 6 years ago

Google claims that the smallpox vaccine was somewhere between 90-97% effective (they didnt do fully controlled studies back in the day)

Keep in mind, that controlling covid is a giant win. We don't need to eradicate it, just get things under control.

threeseed3• 6 years ago

We don't need to eradicate it, just get things under control

Based on what we've seen there is no grey area. Either you fully control it which then ends up basically eradicating it e.g. Australia/NZ or you don't and then you end up like EU/US and going in and out of infection waves.

rpedela• 6 years ago

One dose of MMR vaccine is 93% effective against measles, 78% effective against mumps, and 97% effective against rubella. Two doses of MMR vaccine are 97% effective against measles and 88% effective against mumps. MMR is an attenuated (weakened) live virus vaccine.

From:

https://www.cdc.gov/vaccines/vpd/mmr/public/index.html#:~:te....

howlgarnish3• 6 years ago

That headline is not quite correct. From the article:

Phase 3 interim analysis including 131 Covid-19 cases indicates that the vaccine is [on average] 70.4% effective when combining data from two dosing regimens ... In the two different dose regimens vaccine efficacy was 90% in one and 62% in the other

And to be clear, it's not just one dose vs two:

tests on two different dose regimens showing that the vaccine was 90% effective if administered at a half dose and then at a full dose, or 62% effective if administered in two full doses.

So "Oxford vaccine is up to 90% effective", perhaps?

kjakm• 6 years ago

Another article I read seemed to indicate they haven’t investigated the half dose regimen fully so it sounds like until more testing is done that’s not the recommended path (in which case the headline is being generous).

agd• 6 years ago

I think I read (and I may be wrong) that the costs for the vaccines per dose were roughly as follows:

Moderna: £45, Pfizer: £20, Oxford: £3,

The Oxford one is also easier to store and transport.

threeseed3• 6 years ago

Oxford one is also going to be easier to manufacture given that it is based on existing technology.

Many countries e.g. Australia are licensing the formula so this is an important aspect.

singingfish5• 6 years ago

the mRNA style viruses will probably decrease in cost exponentially the same way that DNA sequencing and computer technology have dropped in price.

Nitramp• 6 years ago

I read the opposite - producing mRNA fragments at scale is supposedly cheaper than producing the inactivated vector viruses with the correct payload.

londons_explore• 6 years ago

Considering most economies are losing ~£100/person/day by having everything shut, the cost is fairly irrelevant.

bb1232• 6 years ago

Not for developing countries. And ultimately it is important for them to get vaccinated too, otherwise they will form a huge reservoir of COVID that will inevitably mutate and come back around to us.

pja2• 6 years ago

Yes, the Oxford/AstraZeneca vaccine is much cheaper: https://www.bloomberg.com/news/articles/2020-11-22/astra-oxf...

jpxw3• 6 years ago

From AstraZeneca:

One dosing regimen (n=2,741) showed vaccine efficacy of 90% when AZD1222 was given as a half dose, followed by a full dose at least one month apart, and another dosing regimen (n=8,895) showed 62% efficacy when given as two full doses at least one month apart. The combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70%. All results were statistically significant (p<=0.0001).

Also:

and no hospitalisations or severe cases of the disease were reported in participants receiving the vaccine.

https://www.astrazeneca.com/media-centre/press-releases/2020...

crx07• 6 years ago

Wow, what a fascinating phenomenon. A weak first dose somehow primes the immune system better than a full one?

athriren• 6 years ago

“The thing is, the immune system is very complicated.”

quote from the link here, but for those who don’t want to click through (this article is fascinating though), it is told in the context of a joke which i will post below the link.

https://www.theatlantic.com/health/archive/2020/08/covid-19-...

There’s a joke about immunology, which Jessica Metcalf of Princeton recently told me. An immunologist and a cardiologist are kidnapped. The kidnappers threaten to shoot one of them, but promise to spare whoever has made the greater contribution to humanity. The cardiologist says, “Well, I’ve identified drugs that have saved the lives of millions of people.” Impressed, the kidnappers turn to the immunologist. “What have you done?” they ask. The immunologist says, “The thing is, the immune system is very complicated…” And the cardiologist says, “Just shoot me now.”

m12k2• 6 years ago

IANAD but my guess is maybe a stronger immune response in the first dose makes the immune system respond so quickly to the second dose, that it doesn't have time to get anywhere and interact with enough of the body to have much of an effect. That way a weaker immunization in the first dose leaves more room for the second dose to have a refreshing/strengthening effect. Basically, 1 + 2 > 2 + 0

bluGill7• 6 years ago

Sample size is too small to say that. The vaccine works across all doses, but that is all the data shows.

shoo• 6 years ago

One thing that isn't obvious to me is exactly how `n` is defined, and how that relates to how many people of that `n` were infected by covid during the trial. E.g. maybe n=2,741 people were vaccinated following the first dosing protocol, but perhaps only a small fraction were infected with covid. So the actual sample sizes being used to estimate the efficacy of each dosing protocol may be smaller.

jpxw3• 6 years ago

Yes, they do state that all of the results are statistically significant though, with very low p-values.

aquadrop2• 6 years ago

Is there possible explanation why would first half dose have much better results than full dose?

pessimist2• 6 years ago

This vaccine is an inactive host virus whose payload has been replaced by the coronavirus "spike". It has always been a worry that the body will generate immunity to the host virus and thus make the vaccine less effective. That is a likely explanation for the first-full-dose regimen being less effective.

bluGill7• 6 years ago

Statistical factors: the sample size is so small that it could be less effective and still show up this much more effective.

I hope not, but sadly it is a real possibility that needs further study.

arindamch• 6 years ago

https://www.cnbc.com/2020/10/21/astrazeneca-shares-slide-aft...

What about this news?

camkego3• 6 years ago

This statement seems a big deal: "There were no hospitalised or severe cases in anyone who received the vaccine"

Is that also true of the Pfizer and Moderna trials? Are the various trials measuring 'effectiveness' in the same way? Is there a standard for 'effectiveness' in these Covid-19 trials?

It will take some digging and real effort to compare the risks and benefits of the various vaccines coming to market.

threeseed3• 6 years ago

There were no hospitalisations or severe incidents for either the Pfizer and Moderna trials were was related to the vaccine.

And it's pretty easy to compare the vaccines. It will mostly come down to price, ease of manufacture and ease of distribution i.e. temperature. Given that for the 3 viruses all have no risks associated with their use.

acqq2• 6 years ago

There was one vaccinated but then severe case in Pfizer trial out of 170 cases evaluated where placebo-then-ill cases are included, or 1 from total 8 vaccinated but then ill.

“There were 10 severe cases of COVID-19 observed in the trial, with nine of the cases occurring in the placebo group and one in the BNT162b2 vaccinated group.” (1) “170 confirmed cases of COVID-19 were evaluated, with 162 observed in the placebo group versus 8 in the vaccine group.”

1) https://www.pfizer.com/news/press-release/press-release-deta...

MattGaiser• 6 years ago

Eh, I think speed to manufacture/distribute is more important. The cost of these is trivial compared to social distancing/lockdown.

elric• 6 years ago

There were no hospitalisations or severe for both the Pfizer and Moderna trials that was related to the vaccine.

I think the commenter wanted to know whether anyone who received the vaccine was hospitalized for anything covid related, not for anything vaccine related.

camkego3• 6 years ago

My understanding from the Pfizer press release, and I quoted it, is that there was one severe case in the vaccinated group. Did I miss something?

SpaceRaccoon• 6 years ago

How do we know there aren't long term side effects?

camkego3• 6 years ago

So, the Oxford vaccine stated "... no hospitalised or severe cases ..."

The Pfizer press release states: "There were 10 severe cases of COVID-19 observed in the trial, with nine of the cases occurring in the placebo group and one in the BNT162b2 vaccinated group."

So, zero severe cases for Oxford, and one for Pfizer. Interesting.

Should also point out the Pfizer trial may have had 43,000 participants, and the Oxford one 24,000, so they are different size trials. Also, it's super easy to miss important details when comparing outcomes like this, to do this properly really requires a project or in-depth investigation, not my 15-minutes research effort. :)

Pfizer release: https://www.pfizer.com/news/press-release/press-release-deta...

andi9993• 6 years ago

"So, zero severe cases for Oxford, and one for Pfizer. Interesting." What is interesting? That they probably both have the same rate, and we are seeing a statistical fluctuation because of the low sample number?

ggm5• 6 years ago

The statistical difference between 25,000 and 43,000 samples being... small. Basically, any effect visible at less than 2 in 40,000 might be missed by the 25,000 test.

Seriously, do you think this is a huge difference in quality of measurements?

bawolff12• 6 years ago

Seems like the sample size is probably too small to draw any conclusions there. 131 got covid in the trial, if 70% effective than 39 should be from the group that got the vaccine (i think. Did i do that right given they're combining the two dosing regime)?

Maybe its chance that none of those 39 got really sick. I'm not sure what the age breakdown of trial participants was- were the people in the oxford trial younger? Did the distribution match the distribution from the mRNA trials? I have no idea.

Mumps• 6 years ago

(afaict) You're right about the 39 (risk reduction = 1-39/131 ~= 70%).

But you're less correct about saying "smple size is probably too small" (in general, people really really really need to stop dismissing things based on sample sizes until they actually go through a Power calculation!). Your question about demographic breakdown is entirely valid.

Hospitalization rate for covid is about 228.7 hospitalizations per 100,000 population [0]. Or, more easily interpretted, about 10-20% of cases turning to hospitalization. Taking the more conservative (10%) rate, we'd need 31 samples for a 95% CI and 5% margin of error. Thus, the interpetation is that is it unlikely that the _lack of seeing any hospitalizations in the vaccine+covid-positive group is by chance_.

Hope that helps!

[0] https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidvi...

arrrg• 6 years ago

This is the information we have on the BioNTech/Pfizer vaccine regarding severe cases: “There were 10 severe cases of COVID-19 observed in the trial, with nine of the cases occurring in the placebo group and one in the BNT162b2 vaccinated group.”

Just as a reminder, that vaccine had more than 40k people in each group, with 170 cases of COVID-19 being observed, 162 in the placebo group, 8 in the vaccine group.

As you can see, the sample sizes get quite small, so I’m not sure how much, if anything, this tells you regarding severe cases. There could have been just as well no severe case in the treatment group, just by luck. What would that tell us?

I didn’t find any info regarding severe cases and the Moderna vaccine but I maybe I missed it. Those press releases are hard to read.

My source is Pfizer’s press release: https://www.pfizer.com/news/press-release/press-release-deta...

tialaramex2• 6 years ago

It's about 43k people total, not per group. And I think this was a multi-arm study, they're testing two variables across two population groups - here's the study paperwork:

https://clinicaltrials.gov/ct2/show/NCT04368728

Everybody in all arms (groups) gets a jab, twice, but what exactly what is in the needle varies. The study paperwork doesn't say which placebo was used in this trial (the participants would definitely have been told), sometimes vaccine studies use a vaccine for something else that you didn't need but is presumably harmless (e.g. think of vaccines you take when going somewhere a bit dubious on holiday). Other times they just use saline. Some other groups got higher doses of vaccine.

Anyway, since everybody got stabbed, nobody (as much as possible not even the people giving you a jab) know what's in the needle - everybody gets assessed for side effects. One of the very revealing things about all these studies is how many side effects you get for injecting people with saline. Sore arm makes some sense at least, somebody stuck a tiny needle in your arm - but you'll get headaches, dizziness, flu symptoms even. The mind is powerful.

newsbinator• 6 years ago

I’d like to know if the vaccine stops a person from getting infected, or only prevents the onset of severe symptoms.

bart_spoon3• 6 years ago

Is that also true of the Pfizer and Moderna trials? Are the various trials measuring 'effectiveness' in the same way? Is there a standard for 'effectiveness' in these Covid-19 trials?

Yes, its true that there were no "severe" cases in the other vaccine trials as well.

This statement seems a big deal: "There were no hospitalised or severe cases in anyone who received the vaccine"

It may be. When considering disease severity, we are no longer looking at a pool of people who have been given the vaccine (which is in the tens of thousands for all of these), we are looking at a pool of people who got sick. That means the sample size is reduced to approximately 90-100 for placebo wing of each vaccine, and 30 for ChadOx vaccine arm, and about 5 for Moderna/Pfizer vaccine arms each. That's fairly small.

Seems like the estimated rate of severe cases is around 10-20%. Assuming its 10% (which would mean its harder to identify an actual reduction in disease severity rate from the placebo group), then in the case of Pfizer/Moderna, there would be a greater than 50% chance of seeing no severe cases in a group of 5 infected, vaccinated patients, even if there was no effect on the severity of the disease. The greatest benefit to the vaccine is that they seem to prevent infections substantially, but that also means it will take months before enough infections occur to get some kind of statistical significance on if severity is also affected.

But with this vaccine, 30 cases with no infections is definitely in the realm of statistical significance. I don't have the exact numbers from the trial, but if it indeed is 0/30 vs around 10/100 between the vaccine/placebo wings, it definitely meets the typical thresholds of statistical significance.

It's important to note that, at least according to my understanding, the Pfizer/Moderna trials are measuring symptomatic cases, not doing actual tests on their trial participants. This means that it could well mean that the reason the vaccines appear to be so effective is because they truly are reducing the severity of the disease to the point of being asymptomatic. We just aren't able to see it yet due to the way the data is being collected.

rusticpenn• 6 years ago

Correct me if I am wrong, Oxford uses traditional Vaccine design technique (using a weaker virus and adding spikes or something similar) while Biontech(Pfizer) and ModeRNA use MRNA which is completely new technique (messenger RNA).

This is awesome for more than just vaccinations. Traditionally the groups allocating govt funding to science and industries are very risk averse and this could be one more example where taking risks can payoff.

bawolff12• 6 years ago

I thought adenoviral vaccines were also relatively new. Not as new as mRNA which is bleeding edge, but still i think this would be the first time this technique would be approved for human use should it be approved.

pietjepuk88• 6 years ago

If I remember correctly, the Ebola vaccine is the first approved vaccine to use another virus as a vector. The first one to be approved (by Merck) does not use an adenovirus, but the second approved one (by J&J) does.

Note that approvals of these were late 2019 and the summer of this year. So still very new from an "approved on humans" point of view (although not _as_ new as mRNA-based vaccines). The techniques have both been in development for years and years of course, including determining their safety profiles.

DennisP4• 6 years ago

The article says adenovirus vaccines have been "researched and used extensively for decades."

senectus1• 6 years ago

Is this the sort of Vaccine that protects against infection or against the disease?

alkonaut2• 6 years ago

The tests are for disease. We hope it protects against infection/the ability to spread it. But that's not part of the testing

I don't know how many existing vaccines fall into either category here, i.e. whether there are many vaccines that prevent disease but do not even reduce the ability to spread. Would be interesting to know.

m12k2• 6 years ago

"There were no hospitalised or severe cases in anyone who received the vaccine"

Does anyone know if there's data for this and the other vaccines, whether any of those that still end up infected under the trials have had any of the secondary symptoms such as missing sense of smell, reduced cognitive function, reduced bio-motor functions, cardiac damage and so on? Not dying from a lung infection is obviously the most important, but some of the other organ damage that corona-virus can cause is pretty scary too, and I'd like to know whether the vaccines seem to prevent this too.

ksec2• 6 years ago

Incoming possible Silly, Stupid and Lazy Questions,

1. Are there any vaccine ( of any Disease ) that are 100% effective? Or do we operate ( as I would assume ) something like 5 Nines effective rate and call it 100%?

2. Across all type of Vaccine, what are the average or median effective rate? i.e Should we expect Vaccine to be 90%+ effective in the first place? Or is that a wrong expectation to make?

3. What happens in the case of 10% ineffective, do they take a third dose?

dragontamer3• 6 years ago

2. Across all type of Vaccine, what are the average or median effective rate? i.e Should we expect Vaccine to be 90%+ effective in the first place? Or is that a wrong expectation to make?

Sometimes, vaccines are only 30% or 40% effective, leading to terrible flu seasons.

I don't really know the mean/median/mode, but 90% is really high for a vaccine.

3. What happens in the case of 10% ineffective, do they take a third dose?

How do you know if someone is one of those 10%?

ksec2• 6 years ago

How do you know if someone is one of those 10%?

I would assume everyone have the vaccine and they still get caught COVID afterwards?

Or do I misunderstood what effective means?

BurningFrog• 6 years ago

The flu vaccine problem is mostly that there are always several strains floating around.

A vaccine that is 90% effective against one strain may only be 40% effective against the collective.

twic5• 6 years ago

This has been downvoted, but it's absolutely true - see the table here:

https://en.wikipedia.org/wiki/Influenza_vaccine#Effectivenes...

The best effectiveness of a flu vaccine in the US since 2004 was 60%.

singingfish5• 6 years ago

1. Smallpox vaccine is 100% effective 2. 90% is high. 3. Probably not. Immune systems are weird and incredibly complicated (think even more complicated than the brain).

bawolff12• 6 years ago

I dont think its true that smallpox is 100% effective

photon-torpedo• 6 years ago

Not an epidemiologist, but I think the goal of mass vaccination if to make R drop to well below 1. If everybody is vaccinated with a 90% effective vaccine, then R drops by a factor of 10 (I think) so that sounds pretty good?

MagnumOpus2• 6 years ago

Yes, R is at 1.3 with WFH and other restriction. In March, R was 3-5 without restrictions.

If everyone got vaccinated with 90% effectivity (or even 70%), it would be enough. However, availability won't be sufficient to get to 100% within a year, and compliance seems to be somewhere around 50-70% at most given polls. (There are a huge number of people even in this forum who are antisocial - "I won't get vaccinated until I have seen super-long-term effects, and screw the people who I superspread the disease to".)

Tepix3• 6 years ago

If enough people get a vaccination that is >50% effective, Sars-CoV-2 should peter out.

bjoli3• 6 years ago

Superficially regarding number 2: on a population scale a lot depends on how contagious the disease is. The measles vaccine is very efficient (over 95% after two doses), but still requires something like a 90% vaccination grade to prevent outbreaks. Measles is very very very contagious.

Covid is not nearly as contagious, so to prevent outbreaks it doesn't have to be nearly as good at the same vaccination grade.

For an individual, however, 70% would not feel very reassuring, which is why we need a lot of people getting vaccinated.

Edit: fixed some autocorrect issues. I feel I should add: measles is not at fun, even if you don't have any complications. You become very sick. Serious complications are _a lot_ more common than adverse reactions to the vaccine. Don't rely on other people being vaccinated unless you have a compromised immune system in any way.

ageitgey2• 6 years ago

For an individual, however, 70% would not feel very reassuring, which is why we need a lot of people getting vaccinated.

Agreed, but keep in mind that no one in the Oxford trial who got the vaccine got a serious case of COVID or needed to go to the hospital. So it's only 70%-90% effective (depending on dose) at keeping you from getting infected, but so far 100% effective at reducing severity and keeping you from dying or going to the hospital. So that's a huge positive to keep in mind and yet another reason to get vaccinated.

sgt1016• 6 years ago

On 1 : I think that measles vaccines have to be 95%+ effective, or basically you have no herd immunity to prevent an outbreak and protect (for example) infants not yet immunized. Because, measles is so amazingly transmissible. Other vaccines are much less effective (ie. yellow fever?) but because the diseases are harder to catch they can be suppressed in the population just as well.

Symmetry• 6 years ago

The sort of polio vaccine used in rich countries is almost 100% effective after three doses. I did some spot checking of a bunch of vaccines I'd heard of and most seem to be between 90% and 99% effective so Covid-19 vaccines seem to be in line with expectations. The flu is worse but that's always a guessing game of which strain will be prevalent when they're making the vaccine. I think that's because more doses tend to be more effective and if a single dose doesn't get you there they just give you more doses, like the two doses for the mRNA covid vaccines. Effectiveness here is how many people get sick. You don't know in this circumstance that they're going to get sick until it happens, though maybe you could keep track of everybody's antibody levels compared to what they should be and guess. That would be way more expensive than just giving everybody the same schedule of doses though.

jakozaur2• 6 years ago

Title is misleading. They tested few configurations, we should use the most optimal one, not the average. Much better source: https://www.astrazeneca.com/media-centre/press-releases/2020...

Good:

+ likely 90% effective if we use optimal dosing

+ no significant side effective. Looks better than Pfizer or Moderna.

+ already pre-produced at huge scale, 3 Bln doses in 2021

+ easy to store and administer, just regular fridge required

+ several times cheaper than mRNA

+ more traditional vaccine than novel mRNA, less tail risk in production and scaling up the process

Not good:

- two doses, efficient one month after first injection

- likely public will be confused about efficiency due to dosing regime

afterburner• 6 years ago

The two existing mRNA vaccines touted earlier also require two doses.

tzs2• 6 years ago

I wonder what happens if you get two doses, but not of the same vaccine?

bawolff12• 6 years ago

Interesting its cheaper than mRNA, i thought that was one of the benefits of using mRNA, was that it was supposed to be cheaper to manufacture.

disgruntledphd22• 6 years ago

I don't know much about the chemistry, but most new processes tend to be more expensive due to setup costs.

andylynch3• 6 years ago

In theory mRNA will be, but it’s a new technology so still going to be more expensive to start with.

The other major benefit is that these vaccines can be developed more quickly, which is worthwhile in its own right.

garmaine2• 6 years ago

I don’t know why mRNA would be cheaper to manufacture. It is far less stable and therefore harder to work with.

lultimouomo• 6 years ago

My understanding (which might very well be ridiculously wrong) is that mRNA vaccines are a bit like 3d printing; it is incredibly faster and cheaper to build a single one-off item, but if you need to mass produce you still want to go with injection moulding.

fabian2k• 6 years ago

One big difference is that RNA is more generic. Within certain parameters it doesn't matter which specific RNA sequence you produce, it always works the same way and you can use the same facilities for this. There are potential cost advantages there, if you can use a generic, validated process to produce different types of vaccines or drugs without having to develop, tune and certify the core production from scratch every time.

I don't know the economics here, but I would assume that cost advantages are much more likely to appear for small-scale products here than what we have now, producing a billion doses in large factories.

OJFord• 6 years ago

If you're manufacturing something and selling it at a profit, that's absolutely a benefit!

I don't know that the manufacturing costs are less (for Pfizer, Moderna), but I think it's a fair assumption that the bulk of the difference is AstraZeneca (currently) providing it at cost.

jpxw3• 6 years ago

Another entry in the “good” column: no hospitalisations or severe cases of the disease were reported in participants receiving the vaccine.

I agree about the confusion, though. I worry that people will avoid this vaccine, in the hopes of receiving the Moderna/Biontech one instead.

That would be a real shame, because the results here are extremely positive. The media’s reporting of this is concerning.

freeone30002• 6 years ago

Due to the low sample size, it's unclear whether there were no severe cases due to the vaccine -- it's likely that there would have been no severe cases in a given group of 39 COVID-positive individuals even with no intervention.

usaphp• 6 years ago

Is that the same vaccine that was approved in Russia? I remember Russia was working with AstraZeneca on their vaccine, but not sure if it's the same one.

fakedang2• 6 years ago

No, the Russian one that was released for public use was developed by one of the government institutes (which has a very shady history of falsifying data).

Tepix3• 6 years ago

has a very shady history of falsifying data

Source?

andy_ppp• 6 years ago

I find it a bit weird that there are fewer asymptomatic cases with this vaccine? Is it somehow increasing the immune response to COVID-19?

foota2• 6 years ago

Maybe the vaccine happens to work more effectively in people that would otherwise have had an asymptomatic infection?

twic5• 6 years ago

The whole purpose of the vaccine is to increase the immune response to COVID-19.

SamBam2• 6 years ago

That's exactly what a vaccine, any vaccine, does.

A vaccine is something that primes the immune system, so that when the real virus enters the body it is attacked and destroyed quickly. This means that the virus can never start multiplying in the body and shedding to other people.

I don't believe there is any modern vaccine that doesn't reduce or eliminate asymptomatic spreading of the disease.

mssundaram2• 6 years ago

Whooping cough. That vaccine causes suppressed symptoms and people can unknowingly spread the bacteria

skocznymroczny2• 6 years ago

The whole concept of 'asymptomatic cases' is dubious to begin with, most likely promoted to increase belief in PCR tests and the whole "new normal" environment.

protoman30003• 6 years ago

While we now get the results from various COVID-19 vaccines I see a societal issue brewing up. How will we deal with the perceived uncertainty of the safety of these vaccines and the surrounding (dis-)infodemic?

I read recently that in some European country (was it Germany?) the willingness to vaccinate against COVID-19 went down from 80% to 60%. With these numbers policy makers will have a hard time convincing the broad population that they can rely on a due process and be safe. In the meantime there is a proliferation of false information and fake news, while in the past there was not much media coverage of significant side effects from a rushed swine flu vaccine [1].

[1] https://www.vox.com/2015/7/27/9047819/H1N1-pandemic-narcolep...

prox2• 6 years ago

Just from a software perspective: never install the big version upgrade. Usually the X.0 versions still has bugs that only come out at huge roll outs. I am inclined to wait a few months to let early adaptors test the vaccine.

Medicine is a bit different though and every country probably has institutes checking the vaccines independently. A lot of eyes are on this probably. No company wants to be the company that botched the corona vaccine.

protoman30003• 6 years ago

That option might not be available in the short term. Spain for example aims to vaccinate almost the whole population until summer 2021. What are you going to do when you don’t think it’s version X.1 yet?

chippy2• 6 years ago

It's likely that the majority of people on HN are not going to be early adopters, and that other groups will get the jab first.

It depends what's more effective, as these groups are all different: do you jab first those who can most easily spread it, those who would most easily get it, those who would most severely be impacted if they got it, or do you jab those who are most diligent, enthusiastic and first in the queue?

I'd even wager that most healthy adults around the world will not be getting the vaccine (but that might be a negative story to run with) but that's at less odds than just healthy, enthusiastic, low risk people getting the jab first.

Guthur• 6 years ago

For me it's a simple risk proposition, how much at risk do I feel my children or I are from covid. For my children it's a slam dunk; their risk from covid is statistical non existent and weigh that against vaccines that may or may not have long term negative impact on them.

protoman30003• 6 years ago

From my perception it’s not that easy. Recently there have been research papers released that estimate long term effects also with children comparable to young adults. For the sake of argument, let’s assume they are right and that we know that COVID-19 has significant long-term risks for children. How do you outweigh that against the uncertainty of risk of the vaccine?

alkonaut2• 6 years ago

This issue seems to solve itself. When the risk is higher/more unknown in the early stage, groups that have high/known risk with Covid can take the vaccine. As time passes, more and more data will be gathered on the vaccine risk so the group that can make the correct statistical call to take the vaccine grows. Whether healthy children will take it in 1, 2, 5 or 10 years deepends on what the statistics turn out to be and whether it's required to protect others.

mhandley• 6 years ago

For me, it's not quite so simple as that. I will vaccinate my children, partly to protect them (though the risk to them is low, as you say), but mostly to protect me and my wife, and more importantly our elderly parents. None of the vaccines are 100% effective, and if I can reduce the chances of my kids bringing Covid into the family, I will.

By the time the vaccine is available for my kids, hundreds of millions of people will have already been vaccinated, and there will be very extensive safety data. Part of the requirements for emergency use authorization is extensive monitoring of safety, so if there's any problem with one particular vaccine, it will be known by then.

jsnell• 6 years ago

Just to be clear, you have no solid evidence on the long term negative impact on children for either the virus or the vaccine. We have no long term data on anything related to this disease.

But for the deadly virus you interpret the lack sufficient evidence on children as no risk, for the vaccine as as a sign of risk. How do you justify that inconsistency?

LandR• 6 years ago

If even one gets sick after taking vaccine the media will jump on it and focus on nothing else for days / weeks.

I think getting people vaccinated is going to be a huge challenge.

Tepix3• 6 years ago

As long as there is a shortage of doses it shouldn't matter too much.

chippy2• 6 years ago

It depends what's more effective: These groups are different: do you jab first those who can most easily spread it, those who would most easily get it or those who would most severely be impacted if they got it.

I think whilst we all want to be safe, ultimately in a year or so, most of the population won't be getting this shot on a regular basis.

markvdb3• 6 years ago

Why do they sabotaged their own messaging by using the 70% number? Reading further, it looks like the vaccine is 90% efficient.

Also, "There were no hospitalised or severe cases in anyone who received the vaccine".

Can we infer anything from that statement? They seem to be suggesting that the infection might be less serious in the vaccinated population...

cinntaile• 6 years ago

It would be a pretty lousy vaccine if the side-effects of the vaccine were as bad and as common as getting the actual disease.

Why the downvotes? I'm answering the question that is being asked. The study is talking about the side-effects of receiving the vaccine.

"Also, "There were no hospitalised or severe cases in anyone who received the vaccine".

Can we infer anything from that statement? They seem to be suggesting that the infection might be less serious in the vaccinated population... "

cuchoi3• 6 years ago

The 70% is the combined data, so probably the most reliable estimate. For two high doses, they got 62% effectiveness and for one low and one high dose they got 90%. They don't know why the latter was more effective.

70% is still a great effectiveness rate, specially for a cheaper and easier to distribute vaccine.

yread2• 6 years ago

The problem with adenovirus vaccines is that body might build immunity against the adenovirus as well. So, you give one jab, adenovirus infects enough cells and creates enough antigens, immune systems notices and does something about it, but it also notices the adenovirus and makes antibodies against that, too.

With the second jab those antibodies immediately neutralize the adenovirus so it can't infect enough cells and make enough of the COVID antigens so the protection is not that strong.

The Russian vaccine avoids it by using two different strains of adenovirus for the two jabs

yread2• 6 years ago

Note that only n=2,741 people received the 90% efficient dosing. That's 10+ times less than the mRNA vaccines so the confidence intervals on that number will be a lot wider

markvdb3• 6 years ago

Thank you for that answer. Much appreciated.

dageshi3• 6 years ago

To put it bluntly, who wants to give anti-vaxxers more ammo to make noise with?

"They're lying to you, they claimed it's 90% effective but actually it's 70%".

leg100• 6 years ago

Classical British understatement.

sgt1016• 6 years ago

I think they are being very careful because the press will pick every aspect of this to bits and put the worst possible light on any positive spin as in "the secret plot to fool you into taking the failed vaccine developed by Boris Johnson's old university". There will be active attempts to derail any intervention that mitigates the coronavirus crisis because it suits so many bad actors to do that and it suits a large part of the population who like a crisis.

rixrax• 6 years ago

Is there any research or early guestimates about risks (or benefits) of getting multiple different vaccines for Covid? E.g. What if one gets this, and then later moderna vaccine? Will they fight each other, or work together or is it unknown whats going to happen?

kuu2• 6 years ago

Will they fight each other, or work together

I'm not a microbiologist, but this is not how vaccines work. The vaccines are going to put "something strange" in your body that "resembles" the virus, but it's not the virus (it's either a deactivated version of it, or some proteins which identify it...) and then is YOUR immune system the one which "attacks" this pseudo-virus. In this way, your immune system is learning how to defend to "this kind" of strange agents.

In a future if your immune system sees the virus, will defend you.

If you get the two kinds at the same time, maybe the two doses are too much for your immune system to handle it properly and the side effects may affect you (e.g. you can get fever because your immune system is under too heavy load).

hutzlibu• 6 years ago

Most of the vaccines developed seem to work pretty much the same, by targeting the same spike protein. And I am also far from being a microbiologist either, but I do know that the immune system is very complex, so I would not rule anything out, when messing with it.

In any case, getting the vaccination can (maybe) actually increase your risk of a severe Covid sickness, when you are exposed to real covid virus at the same time.

https://onlinelibrary.wiley.com/doi/10.1111/ijcp.13795

And I have no data for it and I can imagine it being hard to get reliable data about it, but autoimmune sickness is on the rise. I am not sure a quickly hacked together vaccine can rule that possibility out.

djmips• 6 years ago

"In the future your immune system may help the virus." I think they tested for this in the Oxford vaccine but there is an interesting case such as in Dengue where in a subsequent infection you may do worse with antibodies present. https://en.wikipedia.org/wiki/Antibody-dependent_enhancement

twic5• 6 years ago

I'm not aware of any risks.

There are definitely benefits to vaccine diversity. The Oxford ChAdOx1 virus involves putting a modified chimp adenovirus into people. People don't have immunity to chimp adenovirus, so it infects them and delivers the spike protein, which elicits immunity. But that might also elicit immunity to the chimp adenovirus! If that happens, then a later does of the vaccine - say, for a new strain of SARS-CoV-2 in a year or two - might not be as effective, because immunity to the chimp adenovirus will stop the vaccine delivering the spike. In that case, having a different way to deliver a vaccine will be a life-saver.

jashephe• 6 years ago

Indeed. Maybe someone with more expertise can chime in — it's not clear to me if getting a vaccine with the chimp adenovirus backbone would preclude the possibility of getting another vaccine based on that backbone in the future (because of immunity to the backbone).

ggm5• 6 years ago

Contrary to some views here, I am very heartened by a press release which doesn't gild the lily. This restores a lot of faith in reporting.

thomond• 6 years ago

"gild the lily" = try to improve what is already beautiful or excellent.

ggm5• 6 years ago

70% efficacy at 2c-8c storage for $4 is indeed excellent but many comments here go to "but modena is 95% efficacy whyyyy" and "they're underselling it"

brutus12132• 6 years ago

Does anyone have a pointer on how the mrna vaccine actually works? I understand basic genetics mechanisms and how mrna works inside cells. In shot form, I assume the modified mrna strands are floating through the blood stream. What happens after the injection?

Btw .. I think public health needs to start educating people on how these things work in order to get high coverage. I am alarmed at the number of highly educated people I know who seem suspicious. This fear is just borne by a lack of understanding and can be corrected IMHO.

te_chris2• 6 years ago

I liked this as a background https://www.theguardian.com/world/2020/nov/22/mrna-vaccines-....

This vaccine isn't mRNA though.

ufo• 6 years ago

I kind of is, if you squint. The payload of the adenovirus vector is DNA.

brutus12132• 6 years ago

Thx for the pointer. Yes, I was talking about mrna in the context of the Moderna and Pfizer+B vaccine. This was a good read on why we shouldn't fear reverse transcription. What I still don't get is how free floating mrna molecules in the bloodstream go through the same protein formation process as mrna inside cells. Will continue to search.

te_chris2• 6 years ago

https://www.bloomberg.com/news/features/2020-07-15/oxford-s-... This is a great profile on one of the lead Oxford scientists.

summerlight• 6 years ago

It's interesting to layman's eyes that the dosing regime using 1.5 doses is more effective than the one using 2 doses as I would expect the inverse; are there any plausible explanations for this?

sanxiyn• 6 years ago

One possibility is that 1.5 dosing regime reduces unwanted immune reaction against vector (not payload).

Pfizer and Moderna vaccines are not vectored.

codeulike• 6 years ago

These stats are based on 130 people getting covid out of an experiment of 25,000 people. They dont give a breakdown of the stats (e.g. who was on placebo, who was on which dosing regimen ) but those are small nubmers.

I think its possible that this is just noise. The difference between '60%' and '90%' might just be a handful of cases.

They show that it works though, thats the main thing.

edit: e.g. of those 130 cases lets assume half were in each regimen experiment. So 65 cases in the 'two full doses experiment' if they got 60% efficiacy then that means about 26 people with the vaccine got covid vs 39 with placebo. In the 'half dose then full dose' experiment if they got 90% efficacy then that means about 7 people with the vaccine got covid vs 58 with placebo. So the difference between 60% and 90% is 19 people. They show that the vaccine works but there is lots of uncertainty between the two dosing regimens.

Edit: why the downvotes?

GhostVII• 6 years ago

Only 2700 people were in the 1.5 dose variant.

haltingproblem• 6 years ago

+Gold for the numerical workout :)

cuchoi3• 6 years ago

This comment seems like a reasonable hypothesis: https://news.ycombinator.com/item?id=25184877

bart_spoon3• 6 years ago

One theory is that it's due to the vector. This utilizes an adenovirus (which has been used more commonly in vaccines previously, and is different from the novel mRNA viruses developed by Biontech/Pfizer/Moderna). The thought process is that with a larger initial dose of the vaccine, more immune resistance is built up by the body initially, which then neutralizes some of the booster when its given later.

thehappypm3• 6 years ago

It's because of the way the AZ vaccine works. It uses a different virus to infect cells which then create the antigen to stimulate the immune response. These are a bit unstable, since the vaccine itself, being a virus, is an immune system trigger. The immune system might snuff out the vaccine itself after a huge first dose, then the second dose is wiped out.

This is I think why the mRNA vaccines are doing better. They don't use a virus as a vector, they use a less convoluted vector of a more basic mRNA instruction set. They're also in a way more "scalable" in that a future disease or a mutation of Covid with a new spike protein could have a new vaccine made quickly by tweaking the mRNA sequence.

__warlord__• 6 years ago

In general or specific to Covid-19 vaccines, does anyone knows what happens if you get vaccinated after you got the virus?

ageitgey2• 6 years ago

On one hand, all of these vaccine trials excluded people who already had COVID, so we don't fully know what the effect would be in large numbers. However at least one person with COVID immunity accidentally got into the Oxford Phase 1/2 trial (according to earlier published results), so we at least know it didn't hurt them.

On the other hand, it is generally thought that vaccines can trigger immune reactions that are often much stronger and longer lasting than just being infected, so you would expect there to be a benefit to getting vaccinated even if you already had it. But only time will tell for sure. No one really knows how long immunity of either type will last - we just have to wait and find out!

logicchains2• 6 years ago

On the other hand, it is generally thought that vaccines can trigger immune reactions that are often much stronger and longer lasting than just being infected, so you would expect there to be a benefit to getting vaccinated even if you already had it.

Interestingly the opposite is true for influenza: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870374/

puzzlingcaptcha• 6 years ago

I doubt it would help much, for similar reasons why you don't give a flu vaccine to someone already sick.

A vaccine is meant to stimulate adaptive immunity which culminates in formation of memory cells - highly selected T and B lymphocytes which are very specific to the infectious agent. This process typically takes a couple days [1] and is rather involved. Once you have the memory cells, however, the next time you get in contact with the virus your memory cells will jump-start the immune response much more quickly, before the virus gets a chance to replicate.

In a regular infection the same mechanisms of adaptive immunity are activated, but on top of that you already have the complications from the virus itself (cell death in lung epithelium, accumulation of excess fluid, hypoxia, cytokine storm etc). A vaccine dose won't necessarily speed it up, there are plenty of virus particles already stimulating the immune system - it's just picking up the slack a bit too late.

There are other factors to consider but that's the general idea.

[1] https://www.researchgate.net/figure/Kinetics-of-CD8-T-cell-d...

sgt1016• 6 years ago

An important fact that I haven't seen mentioned in this thread is that 3m doses have been manufactured already and are available in the UK supply chain today. "All" that's required is the approval from the regulator - but I guess that is still a little way off. 3m would do a lot of good though - frontline staff, the most vulnerable, hotspots....

anoncake4• 6 years ago

Were any doses produced yet of the other two vaccines?

est312• 6 years ago

At least in the US, it seems so:

Currently, OWS is working with 11 drug manufacturing companies to produce 800 million doses of six different COVID-19 vaccines, five of which are in Phase III clinical trials. By prepurchasing and premanufacturing these vaccines prior to approval, the vaccine distribution plan can be activated and supplies delivered within 24 hours of any of the vaccines receiving FDA approval.

https://college.acaai.org/updates-on-covid-19-vaccine-distri...

alleskleber• 6 years ago

BioNTech/Pfizer plan to deliver 50 million doses by the end of the year.

https://investors.biontech.de/news-releases/news-release-det...

sgt1016• 6 years ago

I am not sure : I know the other vaccines must be stored at a very low temperature, but does anyone know how long they can be stored for at all?

strombofulous4• 6 years ago

3m worth of working vaccines would do a lot of good, the problem is we aren't sure it works (or even that it doesn't harm you or make you more susceptible)

sgt1016• 6 years ago

More data required - and then approval, I hope.

But you are right, today we don't have all of that information.

standardUser6• 6 years ago

Except that literally all of the data so far says "it works and is safe".

potamic• 6 years ago

India has already made 40m and is ramping up to 100m

https://www.bloomberg.com/news/articles/2020-11-13/india-to-...

peter303• 6 years ago

The Gates Foundation has been capital-sharing with Indian manufacturers to get more vaccine into 3rd world.

christkv2• 6 years ago

I really still hope mRNA vaccines work well and that we keep investing in them. The potential too rapidly create new vaccines and deploy them when needed without requiring a vector will be crucial to counter future pandemics.

Once the oxford vaccine is deployed I suspect they will then have to create a new vector if they need to create another batch in the future as your body might have developed immunity to the vector virus itself making future doses ineffective.

arichard123• 6 years ago

Here [1] it says the vaccine was designed mostly over the weekend of 11th Jan 2020. Here we are 10 months later and we know it works. If our knowledge of vaccine design is so good experts can design a vaccine that works over a weekend, what new breakthroughs are required to reduce the time between then and now substantially? A lot of benefit could have been had if we'd been able to get along this path more quickly.

[1] https://www.theguardian.com/world/2020/nov/23/coronavirus-sc...

jimbokun• 6 years ago

It would require forgoing any kind of serious trials to determine the efficacy and safety of the vaccine.

It is the classic "make a baby in 9 months with 9 women" dilemma. There is no way around conducting a trial and waiting long enough until you see what happens to the participants.

DennisP4• 6 years ago

The main bottleneck is getting a bunch of volunteers, vaccinating them, and seeing how many get the disease over the next few months. Kinda hard to speed that up, unless you're confident/desperate enough to just skip testing. Maybe if the disease were 10X more dangerous and you had a vaccine that was just a minor variation of a previous one, it'd be worth it.

A little time could maybe be shaved off by speeding up production. The mRNA vaccines have an advantage here, you can basically use an RNA printer to churn out whatever RNA sequence you need.

triangleman• 6 years ago

Wait isn't that exactly what they did?

mrtksn2• 6 years ago

Definitely. It’s a similar situation with the aviation too.

Unfortunately, rules in fields like medicine and aviation are written with blood. Someone gets too greedy or too comfortable and you have large numbers of people death or incapacitated.

We already have large numbers of charlatans preying on the hopes of desperate people, must be very careful not to lower the barrier too much or these might jump too. Even worse, people might be targeted by slick psychopaths and coerced into extremely dangerous things, destroying communities when anything goes wrong.

Hopefully though, some mountains might have been moved and some things might have gotten faster from now on.

tinus_hn3• 6 years ago

Yeah, too bad for these millions of people who died from the disease! At least we followed the procedure!

moultano7• 6 years ago

Challenge trials. https://www.1daysooner.org/ If it were considered ethical to do them, we could have known in a few weeks. "Medical ethics" claims another million lives.

tantalor2• 6 years ago

Good summary of problems with challenge trials for Covid:

https://www.statnews.com/2020/06/23/challenge-trials-live-co...

nabla94• 6 years ago

Knowing the efficacy in few weeks is not going to speed up the vaccine trials (see my other comment).

mantap3• 6 years ago

We've subsequently learned that even young healthy and initially asymptomatic people can become permanently ill from so called "long COVID". The ethicists were right to say no.

tinus_hn3• 6 years ago

Considering Russia and China started using their vaccines months ago we could have had the answer anyway. We just didn’t want to look.

nabla94• 6 years ago

Nothing. Timelines for Covid-19 vaccine are already compressed. Even this data is just preliminary from Phase III.

Limiting factor is safety and testing for safety.

They started trials with two people, one gets vaccine one gets placebo. They look for side effects then add more and more people while constantly observing those vaccinated for side effects.

Vaccines are not inherently safe, they are safe because they have gone trough huge amount of volunteer testing. If there are unwanted side-effects, vaccine is withdrawn. Since vaccines work with the immune system, you must look for autoimmune reactions, neurological symptoms etc. Some of them can emerge weeks or months later. With new mRNA vaccines there are even more unknowns.

Emergency authorization they seek means taking calculated risk. With covid-19 epidemic taking that risk is acceptable.

mchusma3• 6 years ago

I strongly disagree with this.

I cannot think of a valid utilitarian argument allowing willing people from getting a vaccine.

First, vaccines have an extremely high success rate, 33% of vaccines make it through all trials to approval. 50% after phase 1 is complete.

The worst vaccine side effect ever is widely considered to be the swine flu vaccine from 60 years ago, where 1 in 100,000 got GBS (a bad disease).

If we knew with 100% confidence that this vaccine was tied for the worst, then if you are over 65 it would be about 1,000x better for you to take this "bad vaccine" versus not.

Each successive trial lost us a lot of time, and very little confidence gain.

The reality is we had many groups all independently find a vaccine that worked in Q12020. It's only the government ban on their use that allowed the pandemic to proceed like it has.

Right now in the US, the FDA has said it is not even planning to MEET on the Pfizer candidate's approval for 3 weeks. Just insane. Then, the CDC says it needs 24-48 hours after FDA approval to authorize it's release. Why can't the meet right now? Why can't the CDC pre approve release? Or be in the meeting and give simultaneous approval? Or be on a phone alert to give approval within 1 hour?

The most likely answer is that in a nationally declared pandemic, any vaccine produced by someone who has gotten a vaccine approved in the last 10 years can sell and distribute (cash only no insurance) vaccines without approval. Require them to collect data on its usage and efficacy. Wait until normal process to require people to be vaccinated.

wbl3• 6 years ago

None. We could have run a 400 person challenge trial in March and gotten the effqcoty data then deployed to Healthcare workers and surveillance for safety. This would entirely change the situation we're seeing now.

Wintamute• 6 years ago

None. Longitudinal trails are required to assess safety - literally waiting and seeing what happens. There's no other way to assess long term effects on the human system. For the avoidance of any doubt none of the new vaccines have had anything like the proper amount of time for a bare minimum longitudinal trial. Whether you decide to take a vaccine nobody in the world is more than 6 months out on will hopefully be left to personal choice.

ta86453• 6 years ago

I find it disheartening how many people speculate about possible long term side effects of exposure to Covid, even in asymptomatic cases. Yet those same people seemingly have no reservations about injecting a brand new drug into their veins.

tboyd472• 6 years ago

Especially when the "gold standard" PCR procedure has a 97% false positive rate.

orzig• 6 years ago

This is asserting that the number of incorrectly positive results is equal to ALL truly negative test takers (https://en.wikipedia.org/wiki/False_positive_rate).

> Citation needed <<

hans1729• 6 years ago

This goes both ways, there are plenty of people who don't take covid serious but fear the health-consequences of vaccines.

There's probably a name for the phenomenon. If not, let me propose "The duality of Hans"

moultano7• 6 years ago

Viruses destroy your cells. Their "purpose" is to do damage to your body. Vaccines don't. If they damage your body it's by accident.

kashprime• 6 years ago

It's a simple choice really; being infected with Covid means your body creates thousands of antibodies to fight the virus. Some of those will likely go on and attack your own cells and cause post-covid symptoms. The vaccines only present part of one protein, so not as many antibodies created, less scope for after effects. Key will be seeing when Pfizer and Moderna release their safety data for their testing cohorts. If the effects are minimal, getting the vaccine is a no-brainer.

ta86453• 6 years ago

Even if you could guarantee that there are no unintended consequences to this drug that was developed over a weekend, which you can't, you must still put a great deal of faith in the motives, incentives, and competence of an entire supply chain.

This is not without risk.

There are a lot of unknowns with this brand new vaccine, yet many of us have personal examples of people in our lives shrugging off a bout of Covid with ease. It's not a completely irrational choice to wait for a few years before taking this vaccine.

ShakataGaNai• 6 years ago

That doesn't really make sense. The two things are quite different. How vaccines work and how COVID works are apples and oranges. Do vaccines have potential side effects? Yes. And of course we don't know them. But let's be honest...most of us regular people aren't getting any of these for quite some time. They are going to go to people on the front line and most at risk first.

If you're a front line worker, like a doctor or nurse in a hospital, your chances of getting real COVID with real damage are very high. The long term effects of that are known to be bad. So any long terms effects of the vaccine are more than likely to be way way less dangerous. Also vaccine is, so far, not lethal which makes it a way better option.

Eventually we, the general population, will learn more about these potential side effects of the vaccines and start to gain access to said vaccines. Until then let's not go all anti-vaxxer and pretend we think vaccines give you autism.

ta86453• 6 years ago

let's not go all anti-vaxxer and pretend we think vaccines give you autism

I agree with most of what you said, but equating rational skepticism with anti-vaxxer paranoia is a bit of a dick move.

Any drug should be approached with great caution, and we should be willing to see its faults even when we're primed to strongly wish for relief from the grip of Covid lockdowns.

notwhereyouare• 6 years ago

Has anybody seen effectiveness numbers? Like if I get this vaccine, is it one and done? Or will it be like a yearly thing.

christkv2• 6 years ago

I don't think we will know that until next winter.

hobofan• 6 years ago

Obviously we can only say it with high certainty for the duration that the pandemic has been ongoing, but there are strong indications that the immunity will more likely be on the timescale of many years (or even decades)[0]. That effect shouldn't significantly depend on which of the vaccines induced the immunity.

[0] https://www.nytimes.com/2020/11/17/health/coronavirus-immuni...

jl27184• 6 years ago

In case anybody was wondering what this actually is: “The ChAdOx1 vaccine is a chimpanzee adenovirus vaccine vector.” They put a corona spike sequence into it.

By comparison, the Moderna is making a RNA vaccine, and BioNTech an epitope vaccine (the actual protein).

The ‘invasive’ effect is decreasing in that order. Oxford’s ChAdOx1 infects your cells to create RNA, then protein, then T-cell recognition/apoptosis, then epitopes trigger B-cell antibody production. Moderna RNA skips the infection part. BioNTech epitopes go right to B-cells.

But, they also have deceasing stability and manufacturing scalability in that order.

xuhu• 6 years ago

Quite a typo in your last sentence.

jl27184• 6 years ago

Ha! I’m leaving it.

thehappypm3• 6 years ago

BioNTech / Pfizer is also mRNA.

rrss• 6 years ago

BioNTech an epitope vaccine

I think BioNTech's vaccine is also an mRNA vaccine.

https://biontech.de/covid-19

Our vaccine consists of a short segment of genetic material, called messenger RNA, that provides instructions for a human cell to make a harmless version of a target protein, or immunogen, which activates the body’s immune response against the SARS-CoV-2 virus

https://en.wikipedia.org/wiki/BNT162b2

jl27184• 6 years ago

Oh interesting. I’ve been following their cancer neo-epitope vaccine research and didn’t notice this was a different process.

shmageggy• 6 years ago

Thanks for the additional context. This is interesting because the has been some worry about the safety of the new and relatively untested mRNA technology, but this makes it seem like traditional vaccines are just that with extra steps. Should that be a license to feel safer about mRNA?

jl27184• 6 years ago

Well I think it suggests a hypothesis for its safety, but real effects are hard to predict in such a complex system.

datameta• 6 years ago

So important: "A key element of Oxford’s partnership with AstraZeneca is the joint commitment to provide the vaccine on a not-for-profit basis for the duration of the pandemic across the world, and in perpetuity to low- and middle-income countries."

jonplackett• 6 years ago

We (Britain) may have totally screwed up our general response to COVID. But at least we’re still pretty good at science. Thanks Oxford for saving the day.

Smaug123• 6 years ago

Tyler Cowen made this point a few months ago (https://marginalrevolution.com/marginalrevolution/2020/07/wh...): the public health response has been "generally poor" but the UK was first on the mark with dexamethasone and has been among the first with the vaccines. He went as far as saying the UK has had the best response to COVID despite the public health response.

ddek• 6 years ago

So, a member of my immediate family is senior management at Public Health England, the civil service institution that should have been planning for this.

When the government announced they were shutting down PHE, in an attempt to copy the RKI (forgetting that PHE is far more than disease control, of course), the RKI wrote a letter to all senior management at PHE. This was quite a confused letter - the RKI didn’t understand why the UK gov were making this decision, when the RKI modelled their processes on PHE. I’ve read the letter.

Add to this, daily squabbles between cabinet office and other branches of government. If there was good news, you’d hear back immediately and you’d be blocked from sharing it. Bad news, cabinet would stall sometimes for weeks.

But ultimately all the guidance was irrelevant because the UK government are not interested in listening to it. When an adviser egregiously broke the rules, a story which dominated the headlines for weeks, they changed the rules. You see it now - the UK isn’t even on the downslope of wave 2, but apparently in 2 weeks we’ll have fans at football games and business as usual.

twoslide• 6 years ago

Also worth noting that we did this by having a board research base that was not tied to immediate returns. A year ago Sarah Gilbert was struggling to get funding for work on the MERS vaccine, which was seen as largely irrelevant.

ssully• 6 years ago

Not to downplay Oxford or Britain's work, but I think it's safe to argue that the poor general response to COVID is also an indicator of your skill at science. And I say this as American, who's response was just as bad or worse.

People are going to look back at this pandemic with amazement at the work the world scientists did to create a vaccine in record time, but with shame and embarrassment at the loss of life in countries that are considered world powers due to politics, ignorance, and stubbornness.

klmr• 6 years ago

it's safe to argue that the poor general response to COVID is also an indicator of your skill at science

This isn’t safe to argue at all. In fact, it’s completely wrong. We know that the poor UK response is almost exclusively due to politicking and government corruption. The scientific advisory panel of the government (SAGE) hasn’t always been right in their assessment but they very quickly produced rigorous working models and solid recommendations, most of which have mirrored (and continue to mirror) the international consensus. Furthermore, public research in the UK has, sometimes against the active opposition of the government, done stellar work to ramp up testing and genetic sequencing.

For instance, several institutes (incl. the Crick Institute in London and the University of Cambridge) had extensive testing capabilities set up in record time, but their offers to official channels were ignored for weeks, if not months (the Crick in particular simply ignored this and already provided testing internally and externally, at a time when basically no country had widespread testing yet).

Likewise, a collaboration of different institutes quickly set up genome sequencing pipelines for COVID-19 samples, and as far as I know the Sanger Institute is sequencing more COVID-19 samples than any other individual entity in the world: https://www.sanger.ac.uk/about/who-we-are/sanger-institute/t...

ska• 6 years ago

but I think it's safe to argue that the poor general response to COVID is also an indicator of your skill at science.

That's not logical at all. It's a reasonable argument that poor general response to COVID is an indicator that you aren't currently doing a good job of governance, but that's a whole different kettle of fish.

Beggers1960• 6 years ago

Beginning to see light at the end of the tunnel, so to speak, with coroanvirus.

Every positive announcement raises my spirits slightly.

mchusma3• 6 years ago

I'm reposting some of my thoughts below to try and genuinely see is someone has an answer to the question: From a utilitarian perspective, why weren't these all approved for the elderly in Q2 2020?

In other words, its May 2020 and you have the option to ban vaccines or allow vaccines for the elderly, what do you pick?

We know the following about vaccines generally: -Vaccines have an extremely high success rate, 33% of vaccines make it through all trials to approval. 50% after phase 1 is complete. -The worst vaccine side effect ever is widely considered to be the swine flu vaccine from 60 years ago, where 1 in 100,000 got GBS, or Pandemrix, where 1 in 18400 got narcolepsy. (1)(2) -Vaccine candidates have 85% chance of making it from phase III to approved (phase III is supposed to be the efficacy check), in other words we expect about a 15% chance that the vaccine is not effective, most of the tests are about safety.

We know the following about COVID: -Unknown long term side effects, reasonably likely to be worse than the worst vaccines ever, but unknown. -The IFR for those over 75 is about 4.6% now(1). Earlier in the pandemic it was about 11.6%(2). -If you assume that people have a 10% chance of contracting the disease, you can say that those over 75 would have approximately a 0.46% chance of dying (4.6 in 1,000 dead) if they don't get the vaccine. This seems to be a conservative estimate.

So if you have to decide whether to ban a vaccine or not in May 2020, and you assume with 100% confidence that this vaccine was tied for the "worst side effects ever", for example it turns out to be as bad as Pandemrix, then you would expect 1 in 18400 to get something like narcolepsy if you give them the vaccine.

Using the IFR and 10% number above, you assume that not giving the vaccine would leave 84.64 dead for the same population. (85x by volume).

I don't know your opinion of "how much worse is death versus narcolepsy?". If you believe death is 10x worse than narcolepsy, then by severity and volume, taking a vaccine with the worst side effects ever would seem about 850x better than not taking it (in elderly populations). Earlier in the pandemic, when IFRs were over 2x as bad, this was well over 1,000x better.

I mean, the numbers so dramatically favor vaccination that I don't get it at all. Why is this not approved already? Why does it take the FDA 3 weeks to even discuss the matter of approval when this made sense to approve in May? Why did all governments opt to ban the vaccines versus allow them?

Sources: (1) https://en.wikipedia.org/wiki/Pandemrix (2) https://www.cdc.gov/vaccinesafety/concerns/concerns-history.... (3) https://www.medrxiv.org/content/10.1101/2020.07.23.20160895v... (4) https://www.nature.com/articles/d41586-020-02483-2

jliptzin• 6 years ago

How many different viruses are there that cause the common cold? About 200? If we can get an effective vaccine for this coronavirus in under a year why aren't we working on all the other coronaviruses and rhinoviruses? I know nothing about biology but let's say it costs $1 billion to develop and test a successful vaccine for a common cold virus, worldwide for $200 billion that isn't that much to not have to deal with colds anymore. Plus it seems like one vaccine might provide protection for multiple different viruses. Or do they mutate too quickly to keep up?

leafmeal• 6 years ago

I would guess that people just don't care enough about getting rid of the common cold. If you're in the vaccine making business, you might as well try and cure some diseases that are killing people. There's more than enough work there already. Also more money...

maxehmookau• 6 years ago

As a trial participant on this vaccine, I'm _very_ pleased by this outcome!

arisAlexis• 6 years ago

Moderna vaccine can be also refrigerated and the efficacy is higher. Something I don't get?

URfejk• 6 years ago

Big Pharma COVID "Vaccines" Are For SYMPTOMS Not The VIRUS: https://www.youtube.com/watch?v=9jEGizsmKLg

Oxford University breakthrough on global COVID-19 vaccine

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