>600M sounds like very very few doses given worldwide population and even western world population.
Which is why people are so keen on getting more vaccines approved (in the US and abroad). Pfizer is targeting 1.3B doses manufactured in 2021, 600M from Moderna, which still leaves the world plenty short (remember each person needs 2 doses). It's a group effort, and there are additional vaccines under development/review that will hopefully contribute to the effort.
There's also discussion around whether Moderna's vaccine can be reduced from 100ml to 50ml while retaining the same efficacy, which would obviously double the amount of doses provided by Moderna.
That's not quite true. You need 2 for full effectiveness, but it's not like missing the second dose leaves you with no benefit at all. In fact, it's far from clear, from a global perspective, that having twice as many people with less-than-full-effectiveness would not better than half as many people with full effectiveness.
That's true, but the FDA EUA specify that Pfizer & Moderna stick to the dosage regime as tested. It's very likely that a half dosage/reduced dosage might be deemed acceptable, but AFAIK no national authority has allowed a dosage regime deviation from what was tested in the Phase III trials. The closest would be the UK allowing upto a 12 week gap between doses of the Oxford vaccine. I agree that it's probably worth it to half the dosage and double the number of people who can be covered when initial supplies are so limited, but till the FDA makes that call, we have to stick to the dosage as specified.
No national authority has had to deal with a world-wide pandemic for the last 100 years. Treating this situation as if it were business as usual and following the normal rules may not lead to the best outcome.
I don't disagree with you, but they also have to balance risk. They need numbers to work on, and those numbers barely even exist right now. The 2K in the Moderna trial who received the single dose is a statistical blip compared to the hundreds of millions for whom the FDA would make decisions.
The EUA is their attempt to manage the health risk to the population - an investigational vaccine using an entirely unproven novel technology stack poses some unbound risk (likely small), vs the benefit of an effective vaccine. Once we change the dosage, the effectiveness also become unclear, while the risk remains (eg, potential trace contamination with precursors in the lipid carriers triggering shock in a untested population subset. Perhaps prescription statins greatly reduce the effectiveness of the vaccine, etc etc). It's the job of the FDA to err on the side of caution and see risks where we would not. I agree with you that the situation is unprecedented, but I also do not blame the FDA for only working with the data they have. I suspect that Pfizer & Moderna will conduct Phase IV trials with different dosage regimes based on which the FDA can modify the terms of the EUA.
I'm not so sure that a less effective vaccine is better than no vaccine at all. If the virus has a less-effective immune response, it could have a better chance of mutating into something that's resistant to the vaccine, in which case all the work creating the vaccine goes out the window.
> “My concern, as a virologist, is that if you wanted to make a vaccine-resistant strain, what you would do is to build a cohort of partially immunized individuals in the teeth of a highly prevalent viral infection,” Bieniasz told STAT. Even rolling out the vaccine at all when there is so much transmission occurring is far from ideal, he said, suggesting it would have been safer to beat down the amount of virus in circulation before beginning the vaccine deployment.
>“You are essentially maximizing the opportunity for the virus to learn about the human immune system. Learn about antibodies. Learn how to evade them,” he said.
Seems clear from my perspective. Two doses are recommend by manufacturers. Anything more or less is pure speculation at best. Why speculate in absence of a way to test your hypothesis?
> Anything more or less is pure speculation at best
There are two lines of evidence. The first is empirical. It It appears that one dose of Moderna _is_ highly effective, perhaps 85% or more. Note the treatment-control divergence after about fourteen days [1]. The second is theoretical. From our ample medical experience with other vaccines, there is strong prior reason to think that one dose is likely to work well, and that a second shot in the distant future would be even better than a second shot after three or four weeks. Booster shots are given a.) as backup for people who don't seroconvert after one dose b.) to trigger a secondary immune response. In light of a.), we shouldn't be surprised by the 85% number (most people seroconvert; there's no partial immunity, you either seroconvert or you don't). In light of b.), we should be very skeptical of the four week interval, especially since the secondary response takes about two weeks to develop. It's shorter than the interval for every other vaccine.
Agreed. It's also important to remember that the 3/4 week dates for the second dose were not chosen based on it being the most effective timeline, but because it was the minimum time needed to complete the studies as quickly as possible. If they'd chosen 8 weeks we wouldn't have US approval yet. If they'd chosen 12 weeks we wouldn't even know if they were effective yet.
The main unknowns aren't around short-term efficacy, but long term immunity. If it turns out that a single dose provides ~80% protection but only for 3 months, whereas the second dose provides strong long-term protection, the one-dose scenario would be significantly worse.
Because the manufacturer recommendations are based on achieving the best outcome for the individual receiving the treatment. But we're in a global pandemic, a situation the world has not faced in living memory. A different quality metric might be appropriate under these circumstances.
So even though the manufacturers (the companies that developed the vaccines, the scientists, the people running the trials, the ones that know the data and went through a full year of tests) keep on recommending 2 doses and the advice given to the UK government was still to stick to the 2 doses, we're now going the way that "we think we know better and it's better to try something new and untested because it's a pandemic and it might be better to have less efficiency to more people, than full efficiency to less people", even though it's, again, not tested and a shot in the dark?
Was there any testing done comparing 2 doses to one? I think it was speculation that led us to test with 2 doses because we'll, we don't have much time, 2 must be better than one.
The study we have of a two-dose COVID-19 vaccine with one dose administered showed 67% effectiveness, in line with vaccines for other diseases (including eradicated ones - polio vaccine is 80%).
Giving one dose increases the probability of someone catching COVID and the virus evolving resistance within this person. I don’t know how likely that is but the impact could be huge.
That the impact could be huge doesn't take much imagination: We could be back to square 1 with the vaccination process and the evolved virus might be more dangerous.
Total production. It's an increase of their previous estimates. It's enough for 300 million people following the schedule studied in the US trial that led to FDA emergency use authorization.
Pfizer projects making more than that.
The AstraZeneca vaccine has much larger production, and the J&J vaccine will also, if it is approved.
My understanding is that both the Moderna vaccine and the BioNTech one are being made in only a couple sites each.
Is there any reason why more labs across the globe couldn't start producing the vaccines, under a license from those companies? Is the technology needed to create them so unique that it literally can't be made anywhere else?
In this particular case the mRNA technology Moderna (and Pfizer) is completely new, these are the first two vaccines approved. Yes they spent a lot (including OWS money) to ramp production, all previous mRNA vaccine production was <1M doses per year in 2019 and before. So between Moderna and Pfizer, we are looking at probably 1.8 billion - 3 billion doses produced.
There are many genuine complaints about the vaccine ramp up, but this is one of the few cases where these numbers are a "good job".
This is why its so important for the FDA to give EUA to Astrazeneca now, that is a technology that can be scaled quickly. They should also encourage a readout now of J&J, which is almost certainly over the efficacy threshold and can also be scaled. With these two approvals, we can have enough vaccine for a 1st dose for everyone within the next 60 days.
The Sputnik adenovirus vaccine is easier to manufacture and they are allowing some countries to install their own capacity. I don't know if they improved the accuracy of their tests, they were kinda sketchy when they announced it.
The PR and marketing is not targeting the US for some reason, maybe because they think no one will want a "Russian" vaccine in the US or maybe because it's more expensive... but in other countries it's going to be "the" vaccine, so I hope it works.
Edit: the Oxford AstraZeneca and J&J vaccines are adenovirus and are nearing completion of their trials, so we are on track for much wider availability.
It's more the difficulty in standing up a new site for GMP (good manufacturing practice). Closest analogy in the tech word would be standing up a new fab, but quite a bit cheaper. It takes time to iron out all the kinks and show that everything is being produced correctly and safely. And skipping this would be disastrous, since we are already reaching dangerous amounts of vaccine hesitancy.
That depends on what the bottleneck is. If it's a precursor or component then more sites won't help at all. Others have commented that it's either vials or clotting factor.
Yes. I've got relatives in the Philippines and they're not expecting to get vaccinated until 2023/2024, assuming the virus doesn't get to them first.
We're amazingly lucky in the developed world and U.S. in particular. Wealth makes it possible to buy up all the supplies (which, reportedly, the U.S. has done) and make sure your people get first in line for it. This is also why the U.S. is both idolized and hated in much of the world.
Which is why people are so keen on getting more vaccines approved (in the US and abroad). Pfizer is targeting 1.3B doses manufactured in 2021, 600M from Moderna, which still leaves the world plenty short (remember each person needs 2 doses). It's a group effort, and there are additional vaccines under development/review that will hopefully contribute to the effort.
There's also discussion around whether Moderna's vaccine can be reduced from 100ml to 50ml while retaining the same efficacy, which would obviously double the amount of doses provided by Moderna.