Vaccine Progress, Approval, and Deployment

[yorksrob]

There are rumblings that the "fill and finish" aspect of vaccine manufacture may prove to be a bottleneck in the roll-out process.

This is precisely the sort of infrastructure that should have been put in place in this country last year. There is no excuse for not being able to provide filling machines, labelling machines, glass, rubber and metal manufacture etc. If we were relying on foreign imports for this aspect of vaccine manufacture, it would be a major failing.

 

[Domh245]

The extended dose interval shouldn't have the same effect as failing to complete a course of antibiotics. If my GCSE hasn't biology let me down:
Antibiotics work by actively targeting the bacteria causing the infection - failing to complete the course means that any bacteria that weren't killed in the first few doses survive and go on to potentially develop resistance to the drug used (in 'active' ways such as developing enzymes to combat the drug or altering their structure and processes so that the drug is ineffective)

Vaccines work by simply triggering the body's own immune response so that in the event of future infections, the body can respond quicker to prevent the virus from gaining a foothold. Failing to take the second dose of the vaccines shouldn't change the way in which the virus mutates (Viruses are 'dumb' - they mutate because infected cells make errors when duplicating them) and so shouldn't have any effect on the effectiveness of the vaccines. The main risk is if there is a mutation that completely changes the 'signature' of the virus so that the body does not recognise it as being the same, but given that with all the mutations we've seen thus far this hasn't been the case, there's no reason to assume that this would happen in future.

The second doses of vaccines are given in effect as boosters to ensure longevity of the immune response in the body (it normally fades away to a much lower level), not as a 'completion'

 

[The Ham]

Just to be clear in regard to this target of mid February to get the top four categories vaccinated, is that with a single dose of what’s supposed to be a two dose vaccine? Whilst I appreciate that one dose offers some level of immunity, will it be enough to significantly reduce the number of hospitalisations and deaths, bearing in mind the profile of the most vulnerable?

Another genuine question as I’ve no idea, does having millions of people walking around in effect partially vaccinated, increase the risk of the virus mutating into a vaccine resistant strain?

If by giving one dose we get a 50:50 chance of getting the virus and we've given it to the people who make up 2/3rds of admissions to hospital then on that alone we'd see a fall of 1/3 of hospital admissions.

However if we then also see a fall in the severity of the illness as well then it could fall even further.

Therefore if we then saw that from the unlucky 50% that they then halved their risk of going to hospital then we'd see a 75% reduction within that group. That would mean an overall fall of 50%.

However even with a 95% protection and a 95% protection from death if you did catch it the fall would be about 65%, assuming that you could vaccinate the same number of people but with two doses.

As such over the short term the difference wouldn't be all that great as although each person would have a higher level of protection fewer people would have that protection.

A late second dose may not provide as high a level of protection, however it may well be that all this means is that those in the very first groups have to have another double dose next year to provide the correct protection.

The problem i have with single (or delayed second) dose strategies is that we are always told we need to take the required course of a medicine as other wise the bug/virus could adapt and render the medicine ineffective. Considering how well this virus adapts and mutates it seems to be a potential time bomb if we play silly buggers, the last thing we want is the virus mutating to make the existing vaccines useless (i know we don't know enough yet about the virus or the vaccines to tell for sure if it could happen but it seems a big gamble to take to be honest).

The vaccine targets the spikes, for the virus to mutate to remove the spikes altogether would be significant (think along the lines of birds evolving away their wings) however it may be possible for the generic code to change enough to avoid detection (think birds evolving a different shaped wing).

However such changes could have other impacts. For example it could be that by changing the code of the spike then it may not be as contagious (like a bird not being able to fly as far or as fast with a different wing shape). Now it could be that it makes it more contagious (giving birds with a poor wing shape the ability to fly further/faster), however that is probably a less likely outcome.

However it should be noted that changes would take many infections to occur and so if we've managed to reduce the spread significantly then such changes become less likely.

Think about it like rolling dice, of we've got to roll two sixes next to each other (a mutation which "beets" the vaccine) the more dice rolls you make the more likely it is that it will happen. If you have to roll twice then 2 sixes next to each other is fairly unlikely, whilst roll it 10 times and your chances improve, roll it 100 times and it's much more likely to happen. In the same way with fewer cases then the risk of it happening reduces.

Yes it's a risk, but it's likely that by reducing the number of cases faster by vaccinating more people then the risk is reduced (as such a mutation may occur anyway, and whilst it may not become so prevalent it may happen even with the correct dosages).

Even if there was a new strain which could avoid the impact of the vaccine then a new vaccine could be developed fairly quickly (the Oxford vaccine needed 48 hours to insert the correct generic code).

However with the account of genetic coding which is being done within the UK (about 1/2 of all done worldwide), any such change would likely be picked up fairly quickly.

 

[hwl]

Just to be clear in regard to this target of mid February to get the top four categories vaccinated, is that with a single dose of what’s supposed to be a two dose vaccine? Whilst I appreciate that one dose offers some level of immunity, will it be enough to significantly reduce the number of hospitalisations and deaths, bearing in mind the profile of the most vulnerable?

Another genuine question as I’ve no idea, does having millions of people walking around in effect partially vaccinated, increase the risk of the virus mutating into a vaccine resistant strain?

Mid Feb = first dose only.
The Ox/AZ vaccine is far more effective at reducing hospitalisations and also the level of treatment needed in hospital than it is at reducing minor symptoms / asymptomatic cases, just even on the first dose.
In the published work (Lancet) an 8 week gap showed better effective ness that a 4 week gap at reducing minor symptoms / asymptomatic cases.

== Doublepost prevention - post automatically merged: 5 Jan 2021 ==

The extended dose interval shouldn't have the same effect as failing to complete a course of antibiotics. If my GCSE hasn't biology let me down:
Antibiotics work by actively targeting the bacteria causing the infection - failing to complete the course means that any bacteria that weren't killed in the first few doses survive and go on to potentially develop resistance to the drug used (in 'active' ways such as developing enzymes to combat the drug or altering their structure and processes so that the drug is ineffective)

Vaccines work by simply triggering the body's own immune response so that in the event of future infections, the body can respond quicker to prevent the virus from gaining a foothold. Failing to take the second dose of the vaccines shouldn't change the way in which the virus mutates (Viruses are 'dumb' - they mutate because infected cells make errors when duplicating them) and so shouldn't have any effect on the effectiveness of the vaccines. The main risk is if there is a mutation that completely changes the 'signature' of the virus so that the body does not recognise it as being the same, but given that with all the mutations we've seen thus far this hasn't been the case, there's no reason to assume that this would happen in future.

The second doses of vaccines are given in effect as boosters to ensure longevity of the immune response in the body (it normally fades away to a much lower level), not as a 'completion'

Agreed.
The unpublished blood analysis (that was referred to at the press conference) apparently shows no reduction in specific immune response due to first dose up to 12 weeks hence their confidence in the 12 week interval for the second dose of Ox/AZ vaccine.

The main reason for the shortest possible interval between 2 dose vaccines, is that traditionally the longer the gap the less likely people are to come back for the second (NHS have extensive stats on this), rather than the quality of immune response which is often better with a slightly longer gap (JCVI will also have the data for all the other 2 dose vaccines against other infections).

It would be nice to have some /more actually data on this.

 

[birchesgreen]

The vaccine targets the spikes, for the virus to mutate to remove the spikes altogether would be significant (think along the lines of birds evolving away their wings) however it may be possible for the generic code to change enough to avoid detection (think birds evolving a different shaped wing)..

Thanks that was very interesting (and reassuring).

 

[Nicholas Lewis]

The problem i have with single (or delayed second) dose strategies is that we are always told we need to take the required course of a medicine as other wise the bug/virus could adapt and render the medicine ineffective. Considering how well this virus adapts and mutates it seems to be a potential time bomb if we play silly buggers, the last thing we want is the virus mutating to make the existing vaccines useless (i know we don't know enough yet about the virus or the vaccines to tell for sure if it could happen but it seems a big gamble to take to be honest).

I'd like to know what they are doing to monitor all those that have had the vaccination and surely they have control groups who are being closely monitored again a bit of transparency would help give people confidence.

There are rumblings that the "fill and finish" aspect of vaccine manufacture may prove to be a bottleneck in the roll-out process.

This is precisely the sort of infrastructure that should have been put in place in this country last year. There is no excuse for not being able to provide filling machines, labelling machines, glass, rubber and metal manufacture etc. If we were relying on foreign imports for this aspect of vaccine manufacture, it would be a major failing.

Wockhart plant in N.Wales was given the contract to fill and finish and the plant has an annually capacity of 400m vials so they can easily produce 2m a week but they rely upon bulk vaccine to be delivered (this has to be QA checked for each batch what that involves i don't know) and as you say they need the vials etc to be readily available which outghten to be a big deal as we can millions of bottles a day for food products.

 

[Yew]

The problem i have with single (or delayed second) dose strategies is that we are always told we need to take the required course of a medicine as other wise the bug/virus could adapt and render the medicine ineffective. Considering how well this virus adapts and mutates it seems to be a potential time bomb if we play silly buggers, the last thing we want is the virus mutating to make the existing vaccines useless (i know we don't know enough yet about the virus or the vaccines to tell for sure if it could happen but it seems a big gamble to take to be honest).

I don't think this is a fast-mutating virus, indeed, it seems remarkably stable compared do other respiriatory illnesses.

From what I understand, this isn't like antibiotic resistance, where we rely on killing enough of the bacteria with antibiotics that the body can finish off the resistant strains, it's more that case that either the response will work (and be very effective), or it won't.

 

[MikeWM]

I don't understand the point about mRNA long term effects - it's no more than a different technique to trigger the immune response.

But the technique matters, of course, and a new technique may well have new long-term side-effects.

As I said already, I think the idea is a rather clever one and I think it has the potential to be a very good thing going forward. But I've no desire to be a guinea pig; we need to know more.

The abortion issue is a bit niche, though - especially as the fetal cells used for are from a line taken decades ago.

I agree this is niche and a matter for individual conscience, and I'm not trying to persuade or dissuade anyone based upon it. I only mention it because it is a factor *I* have considered about whether to take a vaccine or not. Personally my conscience on this is uneasy, despite the distance from the issue that you correctly observe (and indeed that 'significant distance' is effectively the argument that the Catholic Church have put forward for saying that it is acceptable, although having read what they have to say on the issue, I'd argue that is a judgement that seems to be based on expediency rather than on Catholic theology).

 

[kristiang85]

This is an interesting snippet from Nature in 2003, when the first SARS outbreak happened. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095144/

This bit in particular is relevant to this discussion:

Coronaviruses are quite sloppy when it comes to replicating their genetic material, making one error for every 10,000 nucleotides they copy — roughly the same error rate as HIV. But coronaviruses have a trait that allows them to weed out mutations as they occur. Rather than relying on a single template genome, the enzyme responsible for copying the viruses' genetic material sometimes jumps around between multiple copies of the viral genome present in an infected cell. So each new genome is actually copied from several templates, reducing the chance that any given mutation will become entrenched in the viral population.

But if one of these jumps is imprecise, a whole chunk of genome can get skipped, resulting in the deletion of part of an important gene. The consequences can be dramatic, particularly if the change affects the protein spikes that bind to the surface of the viruses' cellular victims. For example, in 1984 a new respiratory ailment appeared on European pig farms. It turned out to be a deletion mutant of a coronavirus that previously had infected piglets' stomachs18. The altered spike protein had changed the type of cells the virus could enter. Although the new disease was not generally lethal, it has since spread worldwide and complicated diagnosis of the gut disease.

A genetic deletion may also have helped the SARS virus to make the transition from its animal reservoir to humans. But, if so, it is a different type of change — the spike protein remains intact. Instead, compared with the viral strains found in animals on sale in southern Chinese markets, the SARS virus lacks 29 nucleotides in the gene for a protein of unknown function, which is attached to the inside of the virus's protective coat.

Should SARS return to haunt us, it will probably not remain as stable as it has been so far, particularly if it is attacked with antiviral drugs. Our immune systems could force changes, too. "Once enough people develop immunity, mutations will be favoured, just as you see with flu viruses," predicts Michael Lai, a molecular virologist at the University of Southern California in Los Angeles.

The last paragraph is the part that is most concerning, because now the precedent has been set with lockdowns you do wonder what will happen if it does become a cyclical virus.

Hopefully governments will be happy just living with it now we have the vaccine tech in place, and adding it to the annual vaccine roster if the seasonal cycles do happen...

 

[brad465]

In the below article on the BBC about whether we can "jab our way out of lockdown?", this table showing effectiveness at one dose seems to be promising:

Covid: Can we really jab our way out of lockdown?

A shortage of glass vials, an overload of bureaucracy and lengthy safety checks could slow the UK down.

www.bbc.co.uk

Hopefully the second doses will still be offered no later than 12 weeks after, but those % effectiveness values for just one dose must surely be very effective in reducing deaths and health service pressure if the mid-February target of the first 4 at risk groups is met?

 

[yorksrob]

In the below article on the BBC about whether we can "jab our way out of lockdown?", this table showing effectiveness at one dose seems to be promising:

Covid: Can we really jab our way out of lockdown?

A shortage of glass vials, an overload of bureaucracy and lengthy safety checks could slow the UK down.

www.bbc.co.uk

View attachment 88217

Hopefully the second doses will still be offered no later than 12 weeks after, but those % effectiveness values for just one dose must surely be very effective in reducing deaths and health service pressure if the mid-February target of the first 4 at risk groups is met?

Interesting wording from the BEEB there.

What is it suggesting if we can't. Permanent lockdown ?

 

[HSTEd]

That’s my concern too. Whilst these fears may be unfounded, it does seem as though we’re yet again disregarding traditional thinking and practice. That hasn’t worked out particularly well to date....

Traditional thinking has nothing to say about our current situation given noone has ever tried to terminate a pandemic through mass vaccination using a vaccine developed during the pandemic before.

 

[The Ham]

This is an interesting snippet from Nature in 2003, when the first SARS outbreak happened. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095144/

This bit in particular is relevant to this discussion:



The last paragraph is the part that is most concerning, because now the precedent has been set with lockdowns you do wonder what will happen if it does become a cyclical virus.

Hopefully governments will be happy just living with it now we have the vaccine tech in place, and adding it to the annual vaccine roster if the seasonal cycles do happen...

It a be bored that the highlight section is talking about antivirals (a medicine - which fights the virus for us) rather than a vaccine (which teaches our body to fight the virus).

Once trained our body keeps fighting until the virus is gone, whilst medicine keeps fighting until it's used up. The former is unlikely to have left over virus able to "learn" defenses whilst there second can do.

Think of it like a child doing their homework a vaccine is a parent teaching them how to do it for an hour and authority it's likely to take the child longer they'll be able to cope with the homework and any future times they have to do something like it.

Whilst an antiviral is the parents doing the homework for an hour. If it only takes them 45 minutes and the school moves the teaching on then that's fine, however the child is likely to find that there's problems if the homework takes 90 minutes and there's more on the subject the following day.

Like all analogies it's good big gaps when you think about it too much, but hopefully it will help with the understanding why that last paragraph isn't that big a problem.

 

[DustyBin]

Traditional thinking has nothing to say about our current situation given noone has ever tried to terminate a pandemic through mass vaccination using a vaccine developed during the pandemic before.

Well yes, that’s the point....

== Doublepost prevention - post automatically merged: 5 Jan 2021 ==

It a be bored that the highlight section is talking about antivirals (a medicine - which fights the virus for us) rather than a vaccine (which teaches our body to fight the virus).

Once trained our body keeps fighting until the virus is gone, whilst medicine keeps fighting until it's used up. The former is unlikely to have left over virus able to "learn" defenses whilst there second can do.

Think of it like a child doing their homework a vaccine is a parent teaching them how to do it for an hour and authority it's likely to take the child longer they'll be able to cope with the homework and any future times they have to do something like it.

Whilst an antiviral is the parents doing the homework for an hour. If it only takes them 45 minutes and the school moves the teaching on then that's fine, however the child is likely to find that there's problems if the homework takes 90 minutes and there's more on the subject the following day.

Like all analogies it's good big gaps when you think about it too much, but hopefully it will help with the understanding why that last paragraph isn't that big a problem.

But it does also mention the immune system which I presumed was the part @kristiang85 was referring to?

 

[brad465]

Some concerns appear to be being raised that the South African Covid variant is better able to withstand current vaccines being rolled out:

Covid-19 in South Africa: Scientists seek to understand new variant

There are fears the new Covid-19 variant could be more resistant to current vaccines.

www.bbc.co.uk

Scientists in South Africa say there is a "reasonable concern" that the new variant of Covid-19 sweeping across the country might prove to be more resistant to current vaccines being rolled out in the UK and elsewhere, and warn that it makes the need for a global roll-out of vaccines "even more critical".

"It's a theoretical concern. A reasonable concern… that the South African variant might be more resistant," Prof Shabir Madhi, who has led trials for the Oxford-AstraZeneca vaccine in South Africa, told the BBC.

Prof Madhi was responding to comments by the UK government and scientists. He said a definitive answer would probably come in a matter of weeks, with extensive testing already under way in South Africa.

The concern arises from the fact that the virus here has mutated far more than the variant in the UK, and one of those mutations might mean it can evade attack by antibodies that would normally fight coronavirus.

Vaccines teach the body to mount an immune response - which includes creating antibodies - to fight the coronavirus, should it ever encounter it.

Antibodies are small proteins made by the immune system that stick to the surface of viruses, effectively disabling them. If that ability to connect is weakened, then the antibodies created following the introduction of a vaccine might not be as effective.

Prof Madhi said it was "unlikely" that the mutation in South Africa would make the current vaccines useless, but might "weaken the impact".

While this requires some further research it seems, if this takers hold I think major questions about the whole strategy will come to light if this variant does spread globally and current vaccines prove to be less effective (even if they can be quickly changed for a new variant the cost and reliance of a vaccine to end restrictions needs to be questioned).

 

[Yew]

Ah, the good old COVID approach of "assume everything is much worse than it is, just in case"

 

[hwl]

Ah, the good old COVID approach of "assume everything is much worse than it is, just in case"

Some of the (different to UK) mutations in the new SA strain are in places that might effect vaccine effectiveness (likely to be partial rather than total effectiveness). Unlike the new UK strain hence the concern.

 

[Nicholas Lewis]

PM committed to 15/2 for top 4 levels to be vaccinated.

Today 1.3m across the UK have now received the jab with 23% over 80 year olds now vaccinated.

1000 vaccine locations will be up and running by Friday with 7 vaccination centres next week.

They will issue the vaccination plan on Thursday (overdue but a real positive) and will provide daily updates on progress daily from Monday.

This is good outcome and should help give people confidence that better times are coming. I certainly feel more confident that we are now at the beginning of the end of this situation for the first time since it started but it wont be plain sailing but its worthwhile people just hunkering down for the next few weeks.

 

[kristiang85]

But it does also mention the immune system which I presumed was the part @kristiang85 was referring to?

Yes that's what I meant. Viruses want to survive, and will evolve to find their way round obstacles in their way, as they always have done.

Luckily coronaviruses are slower than most at doing that.

 

[johntea]

I know of a hospital that started doing vaccination yesterday, they got through 80 people throughout the day

Out of interest what happens if they invite you for the vaccine but you decline to have it at the time, will you just get pushed to the back of the 'queue'? For example if I got offered it in January but didn't take it up when would I be offered it again?

 

[The Ham]

I know of a hospital that started doing vaccination yesterday, they got through 80 people throughout the day

Out of interest what happens if they invite you for the vaccine but you decline to have it at the time, will you just get pushed to the back of the 'queue'? For example if I got offered it in January but didn't take it up when would I be offered it again?

I don't know, however it would be counter productive if someone was awaiting a test result (especially if it then came back negative) to then punish them for not having their vaccine when first offered (and you wouldn't want those awaiting test results to be attending somewhere with the potential to pass it onto people in the high risk/older people groups).

 

[Jozhua]

Vaccine rollout is trundling along, we have 1.3 million vaccines after a month of having them available.

Shortages lie not only with vaccine supply, but with glass vials and lab capacity for proper safety checks. Stuff that should have maybe been sorted out months ago?

I see "global supply shortages" quoted a lot, but considering we have had 10 months to prepare, not the best excuse? I. Get vaccines have a shorter shelf life, but glass vials definitely do not.

We may be best looking away from mass testing now and focusing resources on vaccination, if indeed that would speed up the process. Although it may simply be down to equipment, or other bottlenecks that would not be resolved with the re-allocation of lab space & personnel dedicated to testing.

I hope this is a temporary state, perhaps till the end of the month, before mass vaccination becomes a reality.

 

[yorksrob]

Vaccine rollout is trundling along, we have 1.3 million vaccines after a month of having them available.

Shortages lie not only with vaccine supply, but with glass vials and lab capacity for proper safety checks. Stuff that should have maybe been sorted out months ago?

I see "global supply shortages" quoted a lot, but considering we have had 10 months to prepare, not the best excuse? I. Get vaccines have a shorter shelf life, but glass vials definitely do not.

We may be best looking away from mass testing now and focusing resources on vaccination, if indeed that would speed up the process. Although it may simply be down to equipment, or other bottlenecks that would not be resolved with the re-allocation of lab space & personnel dedicated to testing.

I hope this is a temporary state, perhaps till the end of the month, before mass vaccination becomes a reality.

Exactly. They've had months to put in place the whole supply chain.

Next thing we'll find out is "they only make [Insert component] in China, and we're waiting behind 56 countries for the next batch".

As for labs, yes this should take priority over testing.

 

[Crossover]

Do the vials get cleaned and reused, or do they have to have a brand new one for each set of doses?

 

[hwl]

We may be best looking away from mass testing now and focusing resources on vaccination, if indeed that would speed up the process. Although it may simply be down to equipment, or other bottlenecks that would not be resolved with the re-allocation of lab space & personnel dedicated to testing.

I hope this is a temporary state, perhaps till the end of the month, before mass vaccination becomes a reality.

Reallocating resources (space, people or equipment) in test labs will have no impact on vaccination speeds.

There are very large bulk volumes of vaccine already made, the problem is that you don't start to bottle it in large quantities until it is approved.

With the vaccinates they initially roll out slowly in a limited number of places for several days so they can monitor adverse reactions and revise any instructions and procedures before pressing the big go button (allegedly tomorrow).

For the other vaccination centers there is effectively a 2 step process, open centre and start vaccinating at a limited rate and then when everyone is familiar ramp up vaccination rates (higher rates, more teams, longer hours)

 

[LAX54]

Hire some football stadiums, and carry out mass jabbings, using the NHS and Armed Forces members

 

[hwl]

Do the vials get cleaned and reused, or do they have to have a brand new one for each set of doses?

Brand new

 

[Crossover]

Brand new

I presume old ones will go for melting down for re-use then?

 

[DelayRepay]

Is there an actual shortage of vials? I've seen it mentioned a few times including in the media, but nothing 'official'.

Presumably they are something we could manufacture, perhaps by re-purposing existing manufacturing facilities? Just like we had to do with PPE, and NHS ventilators. People will say 'we can't because...', but given that this is a national emergency and should be the country's number one priority, I think we can.

 

[DustyBin]

Is there an actual shortage of vials? I've seen it mentioned a few times including in the media, but nothing 'official'.

Presumably they are something we could manufacture, perhaps by re-purposing existing manufacturing facilities? Just like we had to do with PPE, and NHS ventilators. People will say 'we can't because...', but given that this is a national emergency and should be the country's number one priority, I think we can.

There are a few things we could and should have done in repsonse to this pandemic but haven't. We're told that it's a national (and global) emergency, the gravest threat to humanity in living memory, but when it comes to implementing relatively simple common sense actions the attitude of "nah that's too much hassle" seems to prevail....