Which is why I am getting annoyed as fuck at the self assured and smug articles proclaiming no worries, vaccine will handle it. Reminds me of the mask debacle back in early spring.
I suspect it will be easy to whip up a new batch of mRNA and add it to the current vaccines either as a cocktail of mRNAs or clone them into one piece of mRNA for expression. Actually, that would be true for the DNA vaccines as well.
Great. Now distribute and administer 8 billion doses. Everytime.
Bear in mind that the vaccine uses the full length spike protein, so there will almost certainly be a polyclonal antibody response - in other words, numerous different antibodies that bind to different parts of spike. And there is a separate cell-mediated adaptive immune response.
So it’s unlikely that the vaccine will go from >90% efficacy to zero against the new strain. If there’s an effect, most likely it will be quantitative, some kind of reduction in efficacy. And remember the original objective was >50% efficacy for a worthwhile vaccine.
If the new strain can evade the vaccine, even partially, it will certainly be really bad news. But it’s unlikely to mean total disaster, unlikely to mean that all our current vaccination efforts are completely useless.
I think I’d be much more worried if we get really unlucky and it turns out to also be a more harmful strain. That would be horribly unlucky - even if the vaccine still works on it, a strain that’s both more infectious and more lethal could get to a whole lot of people in the window of a few months before we get most of the population vaccinated.
I think making a new mRNA vaccine really is pretty quick. As I recall they started trials in February? But I’m not sure anyone would necessarily be comfortable just saying - if the first one was safe, this one is too. It’s trials that take time, and I don’t know what kind of trial protocol would be needed.
Perhaps that would be a time when we really should reconsider the ethics of human challenge trials. That’s where you deliberately expose volunteers, rather than just waiting for natural infections to occur.
Even if this strain doesn’t its show the virus has a pathway to defeat vaccines. Which is not good.
It is the nature of such things. If a mutation is beneficial (such as evading bodily defences or spreading more quickly) then that will be selected for and that is an ongoing process for every virus.
However, don’t be too despondent. The real breakthrough of the mRNA vaccines (such as the Pfizer/BionTech one) is not the efficacy of this particular version but more the speed at which this technology can be adapted to mutations that arise.
Were the new strain to be substantially resistant a new version could be turned around and released very quickly.
It doesn’t show that necessarily. The spike protein can only change so much before it no longer works. If the vaccine/immune system is latching on to a part of the spike that’s vital to penetrating human cells then a mutation that renders it safe from the vaccine also makes it incapable of infection.
Commentary from the BioNTech CEO this morning confirming what we have already noted here, it’s unlikely vaccine won’t work against new strain, but
- they are working on it, will have data in 2 weeks
- if needed, modified mRNA vaccine could be developed in 6 weeks
- but unclear what trials would be needed for regulatory clearance
It’s everywhere in the U.K. already.
Pathogens do tend to evolve into less harmful forms, but you need to be careful with this assumption. Fundamentally the only trait that is subject to positive election is higher transmission. Less severe disease tends to go along with that, but only because of the correlation: if an infected person has rapid onset of debilitating symptoms, if they are laid out dying just a few days after exposure, they are just less likely to encounter so many other people before they die.
So there are several concerns here.
(1) This is only a general correlation. It’s possible that a variant could have severe symptoms but gradual onset. In other words, a period when an infected person feels fine and can walk around infecting dozens of other people before it eventually kills them.
(2) Other factors can affect transmission. A mutation could make a variant better at evading neutralizing antibodies, more efficient at replication, etc. So if you’re really unlucky, you can get a variant that is more harmful, but net overall more transmissible due to other factors.
(3) Consider the process of natural selection against a variant that is more harmful and therefore less transmissible. It will eventually be eliminated from the viral gene pool only because it has killed hosts quickly. Depending on the dynamics, it could kill a lot of hosts before it disappears.
Isn’t it likely that the strain is everywhere everywhere now? If this has been moving around the UK since September, I have to think it’s traveled to mainland Europe and the US. Especially if it spreads faster than previous strains. Not to say it can’t have some effect, but shutting down international travel now is closing the barn door after the cows have gotten out.
Almost certainly, we don’t really know when it arose or exactly where it came from but it is clear that it moves quickly. By the time its prevalence and relevance in the SE of England was noted there was already a potential several week window for it to get out to other locations in the country and elsewhere in the world.
For sure it is out there and I’d expect it to bloom in other areas over the next few weeks.
The good thing is that the world has been given a warning about this as quickly as possible so that measures can be taken but, given that it still managed to spread in UK areas with already strict measures, I don’t think it’ll be easily contained.
I’m thinking along the same lines. The adjuvant/stabilizer and protocols will be the same. That may cut out early phase clinical trials. I’m not an expert.
I don’t know either, but in extremis you’d think maybe they could initially assume efficacy, and focus on safety? I mean, if it’s all exactly the same except for 9 mutations, and we know the other one is safe - there’s significantly less risk in a safety trial, and there would be no shortage of volunteers. So maybe a larger trial size for a shorter time.
Yep. That’s what I was trying to say in my post. Nucleic acid vaccines are relatively easy to make. That’s partly why Moderna and Pfizer were leading the pack in the first place.
Yep. A deadly virus needs to have long enough incubation time and/or prodromal period (signs and symptoms start but not full-blown yet) with the person being contagious for it to spread far. For example, Ebola can have a long incubation period and even prodromal stage. But it’s not considered to be contagious until the patient is very sick. At that point their mobility is pretty limited. It’s also not spread through respiratory aerosols. That’s why it was never really a serious threat outside western Africa in 2014. Contagious people simply aren’t going to get on a plane because they’re too sick at that point.
Yep. Maybe a month and that’s it. The phase 3 trials were already pretty short as it is.
I just noticed I say “yep” a lot.
In fact, the more I think about this, I think they’d have people clamoring to participate in such a trial, because the risk reward is much more clearly defined now. I’m low on the list so I’m probably not going to get my shot until mid-year. Even if they went 50/50 with a placebo group, for sure I’d take a 50% chance of being vaccinated now against the small risk that adding the variant mRNA makes it harmful.
I would assume they would do something based on the established procedure for vaccines to be developed for a flu pandemic. Now, because I worked in EU drug regulation it’s much easier for me to find EU documents than it is to find US ones (but you can bet your ass that there will be an equivalent US document for obvious reasons), so I was fairly quickly able to find this:
Which says:
4.3.1.2. Requirements for applications to change vaccine composition (pandemic
strain change) during a pandemic situationWhere a pandemic situation is duly recognised by the WHO or the [European] Union, a variation application [in effect, a drug licence application specific to the pandemic strain] may be accepted to include the declared pandemic strain [attenuated virus] in the pandemic vaccine (‘pandemic strain update’), if appropriate.
As per Article 21 of Regulation (EC) No 1234/2008, it may be exceptionally and temporarily acceptable that certain non-clinical or clinical data on the declared pandemic strain are missing. In the latter, the MAH [Marketing Authorisation Holder] will have to submit the missing non-clinical and clinical data within the time limit set in the marketing authorisation.
My bold, my explanations in square brackets.
So the TLDR is, tell you what - launch it first and do the missing preclinical stuff and clinical trial stuff asap.
Things to take into account:
- Marketing Authorisation = Drug Licence
- This is talking about a flu vaccine which uses attenuated virus strains to provide immunity, so the situation (at least in re currently used and near-use COVID vaccines) isn’t directly comparable.
- This guidance document is considering a situation where an existing flu vaccine is changed by subbing in an antigen for the pandemic strain (that’s why it talks about a Variation to a licence) rather than dealing with a significant mutation to a virus.
- I haven’t found it yet but there will certainly be (as you would expect) stringent requirements for enhanced pharmacovigilance (post-marketing safety follow up and adverse event logging)
Any questions (re procedure) feel free, I’ll do what I can, but I’ll likely answer from a European perspective.
j
From the various experts in EU nations and the US it would seem that one reason that it has been picked up in UK is that surveillance for varying strains is much better established and more of it is done than in other countries, one Italian specialist stated that the UK has bewtter provision.
Reading between the lines I’d have to suspect that it is more widely spread and it has simply not been detected for lack of surveillance.