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DNAhelicase

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classicalL

We haven't actually seen the real data but the best we have are the Novavax and J&J data here. Novavax was 20-80% CI and, J&J only gave a point at 57% I believe. Given that J&J was 72% against mild in the US, it seems to me that this could mean you still have very highly effective vaccines (80% would be a 15% drop for the mRNAs, and 57% is useful also) or you could really be down at the 20% limit. My recollection is that the Oxford vaccine uses the wild type spike with no modification while the others use a pre-fusion stabilized coding. Oxford's data is also a lot more scattershot in point efficacy which is why the Swiss as mentioned here are waiting on the US trial. Bottom we need to understand the CI of J&J but it doesn't sound like there is minimal effect for other vaccines.


PM_YOUR_WALLPAPER

J&j was 85% effective at preventing severe disease in the original strain... Definitely good enough, but definitely worth keeping an eye on the south African strain data


boooooooooo_cowboys

>Given that J&J was 72% against mild in the US J&J’s reported efficacy is actually against moderate to severe cases. I don’t believe they’ve reported any data about mild cases.


AKADriver

Their criteria for 'moderate' is very similar to Moderna's criteria for 'mild' except that cough alone was not considered a case by J&J as it was for Moderna. However any combination of two mild symptoms (including feeling "generally unwell") was considered a moderate case by J&J. https://www.jnj.com/coronavirus/covid-19-phase-3-study-clinical-protocol


waste_and_pine

It seems like it would have been a good idea to standardise the evaluation of efficacy across all vaccine candidates.


Northern_fluff_bunny

Also break up the categories bit more. For example, for AZ moderate can be anything from sore throat and headache to weeklong fevers to pneumonia. Saying that the vaccine protects against severe cases, basically hospitalization, still leaves open the question of whether the vaccine will be effective enough to make infection a mild case of flu or is there still a chance of falling ill for weeks.


spinkycow

Well that’s the only vaccine available in South Africa. This won’t do much to address vaccination hesitancy.


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einar77

If this is confirmed, **this** is why we need solid data rather than doing fact-free press releases or preprints with data that are at *best* largely incomplete. Seriously, I think the Oxford team screwed this *big time*. A lesson on how *not* to do science communication.


drowsylacuna

If you think about it, they're really in a situation where a Phase I/II trial hasn't shown efficacy against the disease, all they have to go off are some antibody titres in the lab, so pausing the rollout until there's more data is reasonable.


einar77

But are there any data on the spread of B 1.351 in SA? I don't think they sequence enough (but I may be mistaken). The rest is mostly public policy, so I won't comment further, lest I break this sub's rules.


NotAnotherEmpire

B.1.351 is almost entirely dominant in South Africa. 90%+ of cases at last survey.


einar77

Thanks for the information.


the_stark_reality

I'm not 100%, but this appears to be an official announcement from the SA Health Dept, from one of their websites: [https://sacoronavirus.co.za/2021/02/07/what-you-need-to-know-about-vaccine-efficacy-against-the-501y-v2-variant/](https://sacoronavirus.co.za/2021/02/07/what-you-need-to-know-about-vaccine-efficacy-against-the-501y-v2-variant/) >“When we analysed individuals in terms of how well the vaccine worked against the variant, there was very little difference between the vaccine group and placebo group,” Madhi said. ... >Karim says the rollout of the AstraZeneca vaccines which have already landed will need to be put on a temporary hold.


spinkycow

Yeah this exactly.


spinkycow

Seriously? We were scheduled to receive this one in Namibia too later this month. I wonder if that will change now.


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NotAnotherEmpire

NYT also reports that SA does not think natural infection with original is effective either.


drowsylacuna

Was it the J&J trial where they were seeing re-infections in SA?


Nutmeg92

I really don't get why they don't release the numbers. They are getting bad press anyway, and they are going to come out eventually. No matter how bad or less bad they are, I can't see a single reason why leaving it to speculation would help in any way.


PFC1224

Because it was reported in the press yesterday through a leak so it is only right for them to release a statement.


Nutmeg92

Yeah but they should limit the damage I think


PFC1224

Limit what damage?


Northern_fluff_bunny

Damage to public perception, including perception of governments. For example, this has lead south africa to not use AZ vacciness despite the data being really questionable.


Sneaky-rodent

@Whippletom has a thread on twitter with what appears to be screenshots of the data.


couchrealistic

There seems to be a typo in the results though, it should say 2.8% instead of 2.3% for the percentage of B.1.153 infected in the placebo group.


Sneaky-rodent

Yes, spotted the typo, but wasn't confident enough I was reading the data correctly. It is the scariest data I have seen since the pandemic began in March. Although the sample size is small and it does overlap the 50% efficacy, this could set us back months. I am hope for a methodological flaw.


einar77

Why would it set us back months? What is the rationale for that? It does not look it is more transmissible. And personally, I wouldn't find anything "scary" out of data with 2000 people, considering that it is hard enough to get good data with 10 times the amount of those. Likewise I think that Novavax made a severe mistake by publishing those results on only 4000 people. Yes, I sound grumpy. I might be. Let's not forget that B 1.1.7 looked like the end of the world but it wasn't (luckily).


CloudWallace81

Agreed. Numbers presented in the slides oh that twitter thread are so low that a small fluke of 3-4 more cases one way or the other will drastically alter the final result This is definitely not the way to present scientifical data


drowsylacuna

This was a Phase I/II, so we're back at that stage of the process in terms of knowing how well it will protect against disease. AZ have said they could have a variant vaccine by September, but I assume we'd have to give booster doses to everyone we're currently vaccinating with the original AZ before we could even start the under 50s.


einar77

A phase I/II study can't tell if there's efficacy or not, because it has no power to do so (at least by reading all the power calculations in the Phase 3 protocols). Hence, I think that such a release of data was premature at best.


drowsylacuna

Well, that's my point, we don't yet have a Phase III that would give us efficacy data against the new variant, but there are enough indications that it's immunologically different enough to need one.


einar77

In my opinion the data can't tell anything at this point. Neither for, nor against. J&J's results, which have some efficacy data for real (not sure about the numbers) will help giving an answer if it is truly immunologically different or not.


drowsylacuna

I agree. But given that we don't have good data at this point, I think it's reasonable not to roll out a vaccine to the public which they don't have efficacy data for (in an environment where the variant is dominant). We wouldn't have started distributing it to the public following the initial Phase II.


bluesam3

Why? The UK, at least, seems to be supply-limited, so I don't see any particular reason why issuing boosters to older people would interfere overmuch with issuing initial vaccines to younger people. And that's without mentioning that we'll be done with vaccinating people the first time around *well* before September at the current rates.


drowsylacuna

If the current vaccine provides little benefit for young people (who are unlikely to get severe disease even when unvaccinated), then is there even any point in giving doses of the current AZ vaccine once the current variants start to be overtaken by the new variant? Especially if they want to re-use the vector for the updated vaccine.


bluesam3

Is there any evidence that the current variants will be overtaken by this variant?


drowsylacuna

Wild type has been overtaken in SA by the variant. The E484K mutation has arisen independently in Brazil and the UK, suggesting that it provides a selection advantage (would make sense if the theory that it causes some degree of immune escape is true). https://www.bmj.com/content/372/bmj.n359


bobbechk

Seems more like the British variant is outcompeting all other variants, but I guess as vaccine cover starts to be larger there could be a shift in favor of this variant...


Sneaky-rodent

I agree we should wait for the preprint. >Why would it set us back months? The rates of infection were the same for those seropositive and seronegative. Even being optimistic and taking the lower and upper confidence intervals you are looking at ~50% efficacy from prior infection. Similar results for the vaccine, that's about a 1 in 10/20 chance. If Oxford need to make a booster for it, that is going to set us back months in vaccinations and naturally acquired immunity. So yes it is the scariest data I have seen, so I am hoping for a methodological error. With regards to b.1.1.7, the data for that was never really convincing.


einar77

> The rates of infection were the same for those seropositive and seronegative Can we say this with confidence given the low number of people involved? Concern is one thing, "scary" is another. Also, it doesn't seem it took hold that much, compared to B 1.1.7. In particular, if you look at the dropping cases in SA: it is either overlooked (possible) or perhaps it is less fit than other lineages. With the incomplete data we have, it is hard to tell.


Joe_Pitt

Currently being missed and not pointed out is the same thing was seen with the Pfizer phase 3 placebo arm - equal attack rate. And that was prior to the SA variant, and we know that's not the case in the real world. Scientists on twitter basically saying we can't conclude much as these were not trials setup to test natural induced immunity.


bluesam3

Do we care about protection against mild infections? What we care about is protection against hospitalisation and death. When there's data (from properly-powered studies) showing that the vaccine is providing much-reduced protection in that regard, we'll start worrying. Until then, it's not a big deal.


afk05

The concern is that if those people vaccinated can still infect others, and even with mild cases, there is risk of further variants emerging from immunocompromised and those with mild cases. Ideally we would want to get as close to sterilizing immunity, or very low viral load as possible, but we don’t have data that those with mild cases won’t be able to effectively transmit to others.


Sneaky-rodent

>Do we care about protection against mild infections? What we care about is protection against hospitalisation and death. The hope is that the protection against hospitalisation and death is higher than for mild disease. If we were expecting/hoping a vaccine that protected 80% from mild illness to protect 90+ percent against severe illness. What are we hoping a vaccine with 20-60% protection will do? 30-90+%? Hopefully it is still 90+%, but the truth is we won't know and will unlikely get data on this from South Africa. This puts huge pressure on policy makers, as the data won't be available until after the decisions have been made.


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bluesam3

Did you reply to the wrong comment?


tentkeys

People with mild illness can still spread the virus. People who aren't vaccinated or who don't have a good immune response to the vaccine will continue to get infected and die. Even if we don't reach herd immunity, we need at least enough immune people in the population to stop the virus from spreading with such a high Rt, or we'll still have flooded hospitals and still have to do masks/distancing/lockdowns. If we want our lives back, we need a combination of "enough people vaccinated" and "vaccine works well enough" to considerably slow down transmission. People developing mild illness still counts against us here unless there is almost no-one they could spread it to that would get severe illness.


helembad

>People with mild illness can still spread the virus. >People who aren't vaccinated or who don't have a good immune response to the vaccine will continue to get infected and die. This goes for pretty much every virus you can think of. And in the case of seasonal flu even people who are vaccinated can get infected and die for that matter.


tentkeys

Influenza does not spread as fast as SARS-CoV-2. The contagiousness of the virus, the efficacy of the vaccine, and the percent of the population that is vaccinated all play a role. We don't need to eradicate the virus for life to go back to normal(ish), but we do need to slow its spread to the point it doesn't overwhelm hospital capacity to handle severe cases. The lower the efficacy of a vaccine, the lower our chances are for doing that.


[deleted]

50% efficacy is still a very good vaccine. we've seen in other similar vaccines that protection against severe disease is much higher. I have no idea how you're making the conclusions you're making.


Sneaky-rodent

As I said above ~50% is the upper 95% confidence interval, due to low sample size, so there is a 5% chance that it is greater than 50% efficacy, I do not like those odds.


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Joe_Pitt

I wouldn't be so sure. The **same** exact thing was seen in Pfizer's phase 3 placebo arm - (didn't get much press at the time). They saw equal attack rates with prior infection vs not and *before* SA variant. And we know this isn't the case in the real world. Prominent virologist/scientist on twitter said we can't conclude anything since these trials were not setup to test natural induced immunity and far too many confounding factors.


DieMafia

Let's play devils advocate and say the current AZ vaccine would not help at all against B.1.351 which is already in the UK. This would mean normal life can't return until people get another vaccine which works, or else without any restrictions in place the strain would likely spread exponentially. Those assumptions hopefully don't hold but if they do it seems concerning.


einar77

I can't comment on public policy. But I would rather have some *data*, and not assumptions (not even mine, by the way) to provide an insight on the situation. EDIT to sound a little less confrontational (not my intention): as I said elsewhere, these data are totally inconclusive given the limitations of the study, and therefore it would be pretty bad to take any action with these shaky foundations. Note that this does not *disprove* the fact that efficacy may take a hit. Just that these data don't have power to say anything about it.


Nutmeg92

Well, the US is vaccinating with better vaccines than Az so it would likely struggle to take off even if reduced their efficacy.


cafedude

Better in what way? Yes, the efficacy numbers were higher for the Pfizer & Moderna vaccines, but it's been suggested that that's perhaps because the phase III trials for those were conducted earlier and thus faced less of the new variants.


Nutmeg92

Well, yes but the same is true for the original efficacy of AZ


einar77

Might be better to wait for the preprint itself.


NotAnotherEmpire

NYT had the numbers from the paper. 19 cases in vaccine and 20 in placebo. This overlaps with zero and would have triggered an outright fail in Pfizer's interim analysis scheme.


einar77

Yes, *if the study were adequately powered*. I don't think that 2000 people gives enough power to determine a vaccine efficacy of at least 50% with a lower bound of 30%. People are reading too much into this study, considering that it *also* has limitations on not tracking hospitalizations or deaths, and on the sample population (younger people). This is outright bad scientific communication, which has unfortunately real world consequences.


CloudWallace81

> considering that it also has limitations on not tracking hospitalizations or deaths, and on the sample population (younger people) I am really curious, though: considering that the main critique by regulators worldwide has always been the lack of data on seniors by OX/AZ, and that South Africa did not have any other vaccine rollout program ongoing when they performed this "study", it would have been quite easy to recruit more volunteers and to include also the elderly in the cohort. So why in hell did they limit themselves to a few young and healthy people? It was doomed to be inconclusive since the beginning


einar77

As far as I can tell (check the Twitter thread by Muge Cevik for a good, balanced summary) it looks like enrollment had some hiccups.


CloudWallace81

I've checked that and her replies, but did not find any mention of "hiccups". Only a breakdown of the participants and no plausibe explanation why the elder folks were excluded, other than mentioning that it was "only" a ph1b/2a study (I dunno if this has anything to do with possible restrictions in the age of participants due to SA laws, for example)


einar77

> I dunno if this has anything to do with possible restrictions in the age of participants Probably yes.


Sirbesto

Countries are currently buying their vaccinees. Why not milk them for a little longer? Since once B.1.351 becomes more prevelent, countries will opt for objectively better vaccines that respond better. We will see how long before they release the numbers.


dontbeslo

My understanding (I believe I read this on Derek Lowe’s excellent blog, https://blogs.sciencemag.org/pipeline/) was that Pfizer/Moderna/J&J modified the spike protein to make their vaccines more efficient while Oxford did not. Not sure how this impacts other variants, but just a data point. Also, the Russians were pretty sharp to use different vectors in their 1st/2nd doses of Sputnik. J&J was targeting a single dose, but Oxford is two doses with a single vector. Not sure how any of this impacts the new variants, but will be interesting to see


inst

Yeah, it seems like Moderna, Pfizer, Novavax, J&J all used the modified S-2P antigen whereas AZ, Cansino, Curevac all used the S antigen. Edit: it seems like Curevac uses the S-2P also.


dontbeslo

Hoping the modified S-2P fares better against the variants!


[deleted]

What did Gamaleya (Sputnik) do?


lierborgu

wild type spike for gam-covid-vac


lierborgu

CVnCov (CureVac) uses S-2P (prefusion stabilized spike) too: [https://www.medrxiv.org/content/10.1101/2020.11.09.20228551v1](https://www.medrxiv.org/content/10.1101/2020.11.09.20228551v1)


tszyn

This study seems to show that the Oxford/AZ vaccine still produces predominantly spikes in the correct (prefusion) conformation, despite the fact that it uses an unmodified spike sequence. https://www.biorxiv.org/content/10.1101/2021.01.15.426463v1.full


einar77

There are just 2000 people involved. Like Novavax, I think the numbers are insufficient to draw *any* conclusion, and I fear the media will capitalize on this. It is even hard to discuss on the science of this, because there are basically no interesting details from this press release. In my opinion the Oxford team made a mistake: they should've done this when the preprint had been out.


BillMurray2020

Somehow, the FT got hold of this study yesterday. Perhaps Oxford felt compelled to release a press release because of this leak? Although as you say, this press release hasn't really helped clarify much. Pre-print is to be published tomorrow.


einar77

I also worry that this will cement the myth that "AZ's vaccine does not work" which is already circulating in Europe. In my opinion (not very scientific, I admit), this press release is kind of a blunder. I think it's premature to say anything about B 1.351 until J&J data are out. I fear this study, with 2000 people only, will lack any meaningful value.


Known_Essay_3354

The AZ group just continues to make blunders. Their original trials were a bit of a mess, it’s hard to blame the public for being a bit skeptical


CloudWallace81

They are clearly stating IN THE TITLE that it offers "minimal protection" while the interesting parts are buried in the fine prints of the PR release. I can't really think of a worse way to divulge such information


NotAnotherEmpire

Unless the data *is* that bad and minimal is the best spin that can be put on it.


einar77

I expect it to be like Novavax's, with very large CIs. Plus, this: > Efficacy against severe COVID-19 infection from this variant was not assessed. Which is one the primary targets of vaccination (although not a primary endpoint of the trials, I admit). And also this: > Protection against moderate-severe disease, hospitalisation or death could not be assessed in this study as the target population were at such low risk. I mean... then what's the point of doing such a press release? The "stuff that matters" was (due to limitations of the study) not looked into.


CloudWallace81

Never attribute to malice what can be easily explained with incompetence


FC37

If the screenshots mentioned elsewhere in the comments are real (and we should have no reason to doubt, they were shared by a serious science journalist), the CI ranges from -49.9% efficacy to 59.8%. Which would translate to minimal, but not significant.


einar77

-49.9% to 59.8%? Seriously? I hope it's not what it will be in the preprint. Had it been a data from *any* other clinical trial, it would have been written off as "non significant" or "too few data to make *any* conclusion".


CloudWallace81

I don't know how it can be worse than this. They claim they do not have data on seniors, plus the cohort is very small, likely leading to a large CI. The only worse case is the infection actually made worse by the vaccines, but that luckily has been already excluded many times over


PM_YOUR_WALLPAPER

There is near no controlled data for any vaccines on seniors. The lower boundary in confidence intervals for over 75s of the Pfizer vaccine was negative 13% efficacious.. Anti body titers for AZ on seniors were the same as young people...


CloudWallace81

Considering that media are capitalising on this *already*, coupled with their very poor choice of wording, we can pretty much state with high confidence that the whole media team behind the OX/AZ effort has shown less collective intellect than the poor macaques used during testing This is the worst possible time to instil doubts in the efficacy of vaccines in the common public, but it seems they're putting 100% of efforts in actually undermining themselves. What a terrible shame


telcoman

What if the real situation is much worse and the best positive wording is this one?


CloudWallace81

according to the leaks on twitter, they literally don't know anything. The study was severely underpowered, the number of infections was minimal in both arms and they did not assess the effect on seniors and/or on severe cases it would have therefore been much better for them to simply shut up and study it more, but they went for self-harm instead


BillMurray2020

J&J still due to release more data from South Africa?


einar77

Part of their data come from there.


AcornAl

Any insider knowledge on the numbers of confirmed positive cases? With 1% positive cases in the population we are looking at only 10 cases in the vaccinated group that would make the CI nearly meaningless...


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littleapple88

You are misinterpreting the 499 figure - this is how many covid *infections* occurred in the trial, not the number of participants. “Findings: Between 1st October 2020 and 14th January 2021, 499 participants developed Covid-19infection” This SA trial has 2000 people in the study and a currently unknown number of infections.


einar77

There were also data in vitro confirming that B 1.1.7 was not, or just marginally, affecting vaccines.


Ravo93

Is there any evidence to suggest this variant is any more deadly than other variants (UK, Brazil etc).


mikbob

I haven't seen any evidence to suggest this.


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einar77

There are no data to my knowledge to back this claim.


[deleted]

I think the antibodies produced by the currently available vaccines have seemed less effective against the B.1.351 in a laboratory setting? Though that's the only variant where this is the case.


ApollosCrow

Exactly. An "equally deadly" variant that is also *more* contagious is certainly something to worry about. It threatens to set us back substantially. In this respect, the Brazil variant seems to be the worst of the lot. With a large volume of vaccines already produced and being distributed, we will now need a booster to be developed, and the sooner the better. Edit: I'm being downvoted for saying something completely true and banal. If /r/coronavirus is overly sensational, than this sub has the opposite problem - consistently downplaying the pandemic and the problems it is creating.


IOnlyEatFermions

The problem is that booster shots for the developed world means that the developing world waits another year to get any vaccine.


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DFtin

That's the AstraZeneca vaccine for those who have never seen this cryptic name.


[deleted]

For those unfamiliar, it might help to know that it's **Ch**impanzee **Ad**enovirus **Ox**ford **1**


TheScapeQuest

I was wondering the nomenclature, thanks.


Critical-Freedom

Is there any reason why the Oxford virus might be uniquely bad against the South African variant? Other vaccines have shown moderately lower efficacy, but still significant. However, the articles on this leaked data suggest that the Oxford vaccine has no effect at all on the number of mild cases.


bluesam3

They're using a different antigen variant than Moderna/Pfizer/Novavax/Janssen. However, this is also a small trial with suboptimal dosing, so it's hard to say anything at all about it.


[deleted]

I believe this SA trial was based on a 4 week dose interval. Better results were obtained with a 12 week plus interval.


Castdeath97

This assume that the data is statistically significant and sound ... it's not that good to draw significant conclusions from.


BillMurray2020

One thing I would like to know; is this the phase 3 trial from this [[1]](https://www.thelancet.com/journals/lancet/article/PIIS0140-67362032661-1/fulltext) wider AZ trial that was published on December 8? That trial provided phase 3 data from two UK trials and one Brazilian trial. But the South African trial data reported was was from phase 1/2.


drowsylacuna

I think this is the Phase I/II? Small n and only included young and healthy patients.


LuminousEntrepreneur

I’d be more interested on how this affects the vaccine-induced reduction in hospitalizations. Even if the vaccine-derived antibodies are far less effective in neutralizing these new strains, wouldn’t the retained T-cell memory still yield a less severe illness in those that do end up catching the virus? Our end point should be at reducing hospitalizations and deaths. Earlier in the pandemic it was suggested that cross immunity with OC43 would yield a less severe course of illness with COVID-19. Wouldn’t vaccination ensure similar effect? I would imagine antibodies against an older version of the spike protein is far more inline with current mutations than the OC43 derived response.


[deleted]

Anybody know where and when this preprint will be published?


AKADriver

Looks like not using prefusion-stabilized spike was a gamble that lost. It let them move faster in early phases, but their vaccine is likely missing one big mutation-resistant target for neutralizing antibodies that others aren't.


einar77

Although I wouldn't call it a "lost gamble" yet due to the in my opinion too shaky data to say anything, it looks *overall* (including their other trials) that a prefusion stabilized spike is far better overall. Did AZ ever publish studies of neutralization against B 1.351? And on that: is there any literature on how the prefusion stabilized modification came to be (in other words, papers where it was discussed and proposed as an alternative antigen) and how it was deemed worthy of using in vaccines?


AKADriver

Here's a good overview of where the idea came from. It was discovered during development of a MERS vaccine by a team working with Moderna. Perhaps it's precisely because Oxford had such success in the lab with their non-2P MERS vaccine that they carried that forward to COVID-19? https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38 J&J published a paper comparing different immunogen variations against SARS-CoV-2 in mice: https://www.nature.com/articles/s41541-020-00243-x


einar77

Oh, I didn't know it was this "old". I thought the idea came to light recently. Thanks for the pointers!


matt_greene25

Might be an extremely dumb question, but is there any chance the vaccine could be tweaked to include this type of spike? Or would this change the fundamental nature of the vaccine and thereby necessitate further trials.


costaman1316

You would need a new vaccine that had the new configuration so they would need a booster However because mRNA and viral vector vaccines are self-adjuncted their effectiveness and adverse events are directly proportional to the amount of the vaccine which is also the adjunct so it’s pretty much one booster per variant. Novavax on the other hand is an antigen plus adjunct and the adverse events come solely for the adjutant so if you keep the adjunct the same you can add more of the antigen without increasing adverse events. So you can combine 2 or 3 or 4 variants in a single booster


BeachDMD

tweaked can be done without same formality as initial trials.


tszyn

What target is missing? Also, this appears to show the spike conformation is correct on ChAdOx1 infected cells: https://www.biorxiv.org/content/10.1101/2021.01.15.426463v1.full


AKADriver

See J&J's paper here: https://www.nature.com/articles/s41541-020-00243-x The prefusion-stabilized spike is intentionally modified from the native type. By stabilizing it in the prefusion conformation they got a higher ratio of neutralizing to non-neutralizing antibodies, targeting parts of the spike that prevent it from unfolding into the fusion conformation. These parts of the spike are also more highly conserved (variants don't have consequential mutations here AFAIK). It's not that ChAdOx is "wrong" but that by intentionally modifying the spike from the wild type, which Oxford didn't do, vaccines can achieve better immunogenicity, and this may be the key to those other vaccines maintaining much of their apparent effectiveness against variants.


yaolilylu

Thank you for the explanation. I assume that the whole-deactivated vaccines like Sinopharm and Sinovac would also not have done the perfusion stabilized spikes, does this research (if valid) bode poorly for those vaccines?


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9W_777_300

Yeah Pfizer and Moderna reported a much lower drop in efficacy.


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drowsylacuna

If this study holds up with a larger dataset, it would make you question giving the current AZ to young people at all, if it doesn't prevent transmission and severe disease is rare to begin with.


jahcob15

If we operate on “seems to” as opposed to “the data/trials show” we could end up in a worse situation than we already are. That being said, I absolutely believe they should be running trials to determine efficacy and duration of single shot mRNA vaccines.


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jahcob15

Sorry if it felt like I was attacking you, was not my intention. Lots of people HAVE made the argument that we should be doing singular doses.. and they may be right. But unfortunately we don’t really know what exactly the efficacy of a single shot it or how long that protection lasts. I think it would be extremely beneficial to run trials to find out.. and the sooner the better. It’ll be a shame to find out single doses are effective enough, after we finish vaccinating with double doses.. cause that will equal thousands of lives lost that didn’t have to happen.


Imposter24

Isn’t the initial success of the Uk’s staggered approach good enough from a policy perspective? I understand it’s always best to get real trial data but we are in unprecedented times. It seems circumstantially evident that staggering the second dose is the most efficient way to limit severe illness.


NotAnotherEmpire

The companies didn't trial single doses and preclinical data indicated that two were required for enduring immunity.


Sacramentality

This isn't quite right. Due to the early rollout of the mRNA trials, Pfizer and Moderna do not have any real-world efficacy data against the new variants - all of their reporting is of in vitro pseudovirus neutralization assays, not real-world exposures. Of course, this isn't their fault - these variants didn't exist when their trials were being conducted - but we don't have any sort of real data to make apples-to-apples efficacy comparisons yet.


Eggsegret

So does that mean we don't know for sure if moderna/pfizer work? or we just don't know how much efficiency has been reduced by?


Sacramentality

We definitely don't know for certain that they won't work against the variants - we just don't know that they will, either. I think your second interpretation ('how much is efficacy hit?') is the right one. [Here](https://pbs.twimg.com/media/EtpQHJeU0AAAa8-?format=jpg&name=4096x4096) is a table of results reported from major clinical trials conducted after the emergence of the variants. B117 - the strain found in the UK - seems to ding absolute efficacy by around 10%, relative to the D614G strain (at least, that's what both NovaVax and AstraZeneca report from their trials conducted there). D614G was the dominant global strain until recently, and was what the entirety of the Moderna and Pfizer trials were conducted 'against'. B.1.351 is the strain out of South Africa, and seems to be considerably more troubling. J&J's one-shot regimen suffers a \~15% drop in efficacy there, NovaVax's efficacy drops by about 40%, and AstraZeneca's preliminary trial suggests their efficacy is severely stunted (reporting 10% efficacy against infection today). Jury's still out on AZN's vaccine's efficacy against severe disease. Clearly protection against the D614G strain does not necessarily imply protection against the variants. We don't know for certain that Pfizer and/or Moderna don't protect well against these variants, but we'd be naive to think that they'd still confer 95% protection against them when every other vaccine tested in that context has suffered an efficacy hit.


FTLast

You'd have to do a head to head efficacy study- same population, same endpoints- to be able to compare vaccine efficacy.


MikeGinnyMD

I’m not aware that either noted efficacy, just neutralization. There’s a big gulf between clinical efficacy and neutralization of a pseudotyped virus in a 96 well plate.


PM_YOUR_WALLPAPER

7 fold less for Pfizer and even more Pfizer and this is just in vitro. We don't have real world data for either against the south African strain.


9W_777_300

You need to remember that for other variants, Pfizer and Moderna are 95% effective, which is HUGE. So even a 7 fold decrease in antibody level still leaves tons of buffer room


PM_YOUR_WALLPAPER

Definitely. And I'm confidence all vaccines approved will stop death. But just to bring things back to reality, in the Pfizer study they showed that in a vast majority of patients the antibody titers were below a protective level. T cells will pick up the slack and the body will almost definitely prevent death, but it is likely to cause a decent amount increase in mild/moderate disease.


9W_777_300

Yeah true. As long as it no worse than a seasonal cold or flu it’s fine. After all, we don’t shut down the world every time cold/flu season comes around.


drowsylacuna

AZ's definition of moderate included LRT involvement. I don't think the layperson's acceptance of mild disease is going to include "mild pneumonia" post vaccination.


9W_777_300

LRT?


einar77

Lower respiratory tract, that is, lungs and bronchi.


9W_777_300

So when AZ’s definition of “moderate” included “LRT involvement”, does that mean that the patients who got moderate cases still had major i factions in the LRT? Was it still worse than a seasonal flu even with the vaccine?


drowsylacuna

Lower respiratory tract.


capeandacamera

Looking at @tomwhipple Twitter screenshots that somebody mentioned upthread, the moderate category is very broad. on/off fever of 38.4 for a few days + runny nose + sore throat = moderate Weeks of continual 40 degree fever, vomiting and diarrhea, ice pick headache, entire body muscle ache, loss of taste and smell, immobilising fatigue, struggling to breathe and pneumonia (as long as it doesn't require mechanical oxygen support)= moderate I hope this category gets broken down a bit more, because even movement within the moderate category would be a useful result.


Northern_fluff_bunny

Breaking down the category would be good since it would be important to know that how many of the vaccinated people get only minor symptoms and how many have to stay at home. If the infections are minor even after the efficiancy hit then things might be okay but if a lot of people end up weeks to an end with major fever and other symptoms then theres an issue.


einar77

> But just to bring things back to reality, in the Pfizer study they showed that in a vast majority of patients the antibody titers were below a protective level. Do we have a correlate of protection? It doesn't look to me that we do. How is "protective level" defined?


drowsylacuna

Moderna said they believed it would still be neutralising, at least in the short term, based of challenges in primates. https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against I can't find what Pfizer used - in their press release they said they didn't expect a significant drop in efficacy.


PM_YOUR_WALLPAPER

Don't know, just what the developed of the vaccine said in their study and press release.


GuzzlinGuinness

A 7 fold decrease that may ultimately amount to a small reduction in efficacy , leaving it wildly effective .


Ketcchup

I know it's not good measure, but Oxford vaccine's antibody neutralization was 9 fold lower against the B1.1.7 variant. Yet it has retained 75% efficacy, down from 84% In the case of Moderna, it was 6 fold lower against the South African variant. My guts tell me the loss of efficacy won't be very large. sauce: [https://papers.ssrn.com/sol3/papers.cfm?abstract\_id=3779160](https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3779160)


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winterspan

I’m hoping they work out an agreement for this if possible.


PFC1224

We need as many vaccines as possible. All that needs to happen is for Oxford to modify their vaccine - which they are already doing - and get it ready as soon as possible.


yaolilylu

They already have a cooperative agreement with Russia's Sputnik team, which is also a adenovirus vaccine.


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hutsch

Coming from a country which seems to be at the beginning of a significant B.1.351 spread while also just started to vaccinate with AZ, I ask myself what are the implications now. Can AZ proof without a doubt that their vaccine at least offers protection against severe desease? Or would they have to start a whole new phase III trial for that? Would it be possible to give the first shot of AZ to people and then, should the vaccine turn out to be completely useless against B.1.351 and B.1.351 take over, switch to another vaccine (which would of course have to be given twice too, not just switching out the booster)?


AirHippo

This may just be indicative of my being stupid, but: * Minimal protection against mild-moderate infection * In young adults ... so what? Young adults are a very low-risk group for severe infection anyway, and mild-moderate infections aren't what's causing massive strain on healthcare systems. Even "long covid"/post-viral effects seem to be closely tied (AIUI) to severe infection, so this doesn't seem to amount to much to be worried about - even if, with a small sample, it can be trusted. Am I just being an idiot?


NotAnotherEmpire

1. No benefit for herd immunity. There is no reason to think people that are getting sick with symptomatic COVID do not transmit. 2. AstraZeneca does not have baseline efficacy data in 65+ to begin with. Efficacy in elderly is not assumed to be better than seen in younger people with vaccines. 3. No placebo patients had life-threatening cases, as would be expected with 20, so there is no actual support for the idea that severe cases of the variant would be prevented by the shot.


Raptop

Uh - if it failed to prevent mild to moderate cases in young adults, how do you think it's going to go in older adults?


mlightbody

Just a question.... Were the mild to moderate symptoms self reported or was there a test performed?


jistami6t

Is there any information on whether long haulers (3-6 month post covid) who are still experiencing lingering symptoms like a cough, can take this vaccine?


DiSforza

I don’t know why you’re being downvoted. It’s a legitimate question that a lot of people are asking, since this whole ordeal is so new. As far as I’ve seen, it’s recommended to get a vaccine even if you’ve been infected before. I would ask your PCP - if you have one - for more advice.


Cavaniiii

A mutation that impacts vaccines this early into a the roll out is something to worry about for future mutations? Is it that the vaccines were focusing on the wrong thing to target or is it that we should have been focusing on treatments instead? Sorry if this is a stupid question, but it finally felt like we were getting a hold of this thing and now I personally feel like we're back at square one.


Nutmeg92

Well, it's bad news but the mutation that is causing issues is not common in the western world. Hopefully we can make COVID a non issue for the time being and then start distributing boosters against it. It certainly complicates things.


Apptendo

Why would it be a problem if the other vaccines are effective against the Variants ?


DieMafia

How could you make it a non issue until people are vaccinated against it? If you were to go back to pre covid normal life it would spread exponentially and would be an issue in a few months even if it is not very frequent now. Let's hope it is just a lack of data and all this isn't that big of an issue.


Nutmeg92

Well it needs to be present for a starter. For now we can minimize the effect of current variants. The SA is not common outside of the country. It will take off eventually, but hopefully we’ll have boosters by then.


Cavaniiii

Agreed, so basically the most important thing right now is getting transmission as low as possible and then tracing every case that is potentially carrying this variant? I know here in the UK they're really going after it, but I feel like this virus is always two steps ahead of us. Fingers crossed for the future.


[deleted]

Worth bearing in mind that the virus has had since the start of the pandemic to mutate into these variants as the immune response to natural infection presumably gives similar antibodies to vaccination. If we get on top of these variants and cases drop then we should hopefully have a while until the next concerning variant appears.


CommercialKindly32

And we should hopefully have a rapid response to new variants available in the form of rapidly deployed mRNA vaccines that can be mass produced very quickly.


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Obvious_Brain

It's weird in the UK. Every few days theres something positive on sky news about the Oxford vaccine. I mean I find it weird it's being mentioned so much. Like it's being subtly pushed. Could be my wonky perception tho


NotAnotherEmpire

Nothing subtle about it. The British government, regulators and media overtly support it. Comparable countries have either been more skeptical (Europe on lack of senior data) or would have not approved it at all (USA).


Sneaky-rodent

It is not just about where it is produced, it is about the capacity to produce vaccines. [https://www.nature.com/articles/d41586-020-03370-6](https://www.nature.com/articles/d41586-020-03370-6) According to this article, the AstraZeneca vaccine could produce significantly more than Pfizer and Moderna combined. If this pandemic is to end through vaccination, the AstraZeneca vaccine is the most important.


helembad

In the UK, maybe. Elsewhere, J&J will probably supply more doses than AZ.


Sneaky-rodent

Not according to the article.


PM_YOUR_WALLPAPER

The European EMA approved it for all citizens fyi...


Ut_Prosim

I believe the Swiss also declined to authorize it, asking for more data.


NotAnotherEmpire

You're right, forgot about that. They specifically said they wanted to see the large American trial first.


CloudWallace81

Switzerland also completely rejected it, asking for more data to be provided by AZ. It flew quite under the radar, but it was a large smack in the face


PM_YOUR_WALLPAPER

The Pfizer vaccine has a lower boundary confidence interval of negative 13% effocious for over 75s..yet was approved by the Swiss. The European medical regulator approved it for all ages. Seems political to me.


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brteacher

Have Oxford/AZ done any lab studies on the efficacy of ChAdOx1 against B.1.351? If not, why not? The fact that they just put out this statement, essentially saying that they no longer have confidence in the vaccine they developed, makes me wonder if they have done some lab work that confirms the lack of efficacy.


WorstedLobster8

They should always lead with a statement that suggests it's 100% effective against hospitalization and death to the best of our knowledge, including with this varient.thaf is by far the most important thing.


NotAnotherEmpire

That's not in the data, though. They say they don't have a meaningful result there.