Hacker News Reader

Comment by gravypod | Hacker News Reader

Vaccine development has progressed far faster than I would have ever guessed. This might be a dumb question but what has enabled a COVID-19 vaccine to be developed in such short time? I was under the impression that developing a vaccine took on the order of 10s of years while this has been put together in 10s of months. I was also under the impression that this was because making vaccines for viruses was much harder than other treatments because interrupting the viruses reproduction chain is essentially requiring you to interrupt your cell's reproduction chain.

Is there some tool that has been used here that hasn't been available in the past? I know the FDA said they would allow skipping some preliminary testing to fast track a drug. Was that a huge help?

View on HN

SARS-CoV2 is quite similar to the previous SARS virus, so the development for vaccines against that one could be reused. In this case the target was already known, every vaccine is targeting the Spike surface protein. So the existing knowledge allowed them to mostly skip the very first phase of development.

The mRNA platform the BioNTech/Pfizer and the Moderna vaccine use is new, and that is generally something that can lead to shorter development.

As far as I understand, the biggest difference here is simply doing more things in parallel that you usually would do sequentially. This adds more risk because you already waste money in later expensive steps that are unnecessary because a previous step turns out to already fail the vaccine candidate. The easiest example here is producing the vaccine before phase III trials are completed, that is pure risk (in part assumed by governments in this case). This is really a case of "money is no object", a vaccine is useful enough in this case that you can take a lot of financial risk and pour lots of resources into development compared to a less critical vaccine.

The other thing that the more pessimistic timelines assume is that not everything will work out. Any problem can delay a vaccine or kill a candidate entirely.

I know nothing about vaccine development, but I'd guess part of the answer is "It mattered."

People try way harder when the stakes are high, and everyone involved is at least a little terrified of being "the one who delayed it." That does wonders for cutting through pointless red tape and bureaucratic delays.

A minor example:

About ten years ago, a flash flood completely destroyed about thirty linear feet of the main road connecting the tourist district of Hershey, Pennsylvania to the rest of the town.

I assumed it would take weeks or months to repair, based on how long road work has usually taken in the area. It would have been a disaster for a lot of the local restaurants, economically.

IIRC, two days after the flood the road was back in order. It certainly didn't take more than a week.

Obviously, inventing a new vaccine is orders of magnitude more complex than fixing a road, but I think this aspect of human nature still applies.

I wish we’d apply this same level of effort to a better vaccine for Dengue. That’s a problem that’s only going to get worse as the world warms.

The same analogy applies to the 2017 I-85 bridge collapse in metro Atlanta (2017). https://en.wikipedia.org/wiki/Interstate_85_bridge_collapse

This was the main interstate connecting the suburbs to the business districts in Atlanta. The traffic on alternate routes after the collapse was apocalyptical. However, the new replacement was built in record time (1 month). The teams were given cash bonuses and other incentives to finish ahead of schedule. Basically, when "it matters", things get done quicker.

The difference is we know how to make the bridge, and knew where to place it. A lot of the effort in a new bridge is work that didn't have to be done for that bridge because it was already done. No need to figure out what to do with traffic (which means no phases that must complete first). No need to dig new footings, just use the old ones. No need to do a new design - the old one was good enough.

The bridge collapsed because of a fire and there seems to be no reason to redesign bridges to resist a fire like that so a lot of effort was saved. If we decided fires were too common we wouldn't be able to replace bridges as quickly because we need to do engineering work first on a new one.

We know a lot about making viral vaccines too so we have a lot of companies so a couple different methods get used and at least a few of them pan out. It's like if we could have 20 companies try to build the same bridge without interfering with each other and whichever worked became real.

There's been a ton of research on mRNA techniques. This crisis just meant that they got an open cheque book to complete the job.

If these things work as they appear to do, it'll be even more impressive than putting a man on the moon.

Yes, specifically for cancer. I believe both Moderna and Biontech were working on it for cancer treatment.

BioNTech was doing various phase-one trials for cancer treatment. I don't know about Moderna.

They talk about this being entirely self-funded. I wonder about the lack of a cold vaccine - presumably the value would be enormous in terms of avoiding lost productivity. I’ve always been under the impression that a vaccine for the “common cold” is very difficult because of its rapid mutations, mRNA or not. I’m curious why COVID is going to be much different.

Early on I remember an epidemiologist/virologist interviewed on JRE saying that building a point-in-time vaccine isn’t difficult, building a human-safe vaccine with long term efficacy is what’s difficult.

Vaccination is not without risk. Sometimes, but rarely, people have bad reactions to vaccines.

The ethical case for vaccinating against rhinoviruses isn't really there, even if it were viable to do so.

There is a good reason to develop at least one rhinovirus vaccine, though: so we have the expertise to deal with a bad rhinovirus strain if one should arise later. The coronavirus experience - SARS, MERS, and now COVID-19 - seems to suggest that such groundwork on common virus types would be a good idea.

Quite a few things actually.

From President Trump in May 2020 [1]:

> Then, my administration cut through every piece of red tape to achieve the fastest-ever, by far, launch of a vaccine trial for this new virus, this very vicious virus. And I want to thank all of the doctors and scientists and researchers involved because they’ve never moved like this, or never even close.

> The NIH and HHS have also been working constantly with private industry to evaluate more than 100 potential treatments.

> The Food and Drug Administration has swiftly approved more than 130 therapies for active trials; that’s what we have right now, 130. And another 450 are in the planning stages. And tremendous potential awaits. I think we’re going to have some very interesting things to report in the not-too-distant future. And thank you very much to Dr. Hahn.

> Through a historic series of funding bills, my administration is providing roughly $10 billion to support a medical research effort without parallel. I especially want to thank Senator Steve Daines of Montana for his incredible work. He has worked so hard to secure additional funding for vaccine development. He has been right at the forefront.

He also goes on to discuss Operation Warp Speed [2] which, as far as I understand it, creates trials and determines a distribution plan.

[1]: https://www.whitehouse.gov/briefings-statements/remarks-pres...

[2]: https://www.hhs.gov/coronavirus/explaining-operation-warp-sp...

You have a lot of downvotes but no responses. Seems like the government actually supported this vaccine effort pretty well, I don't understand the problem.

I don't think people were downvoting because the government didn't provide support for the development of this vaccine, but because OP was quoting an extremely unreliable source on this topic.

Also a source that's trying to claim personal responsibility for the successes of others, where none is deserved. A government that had the capacity to develop treatments but choose not to would have been in dereliction of their duty; if there's ever been a clear, classic case for communal response, this is it. Claiming as success a response that only partially obstructed dealing with the virus is obscene; and even the parts that appear to be well-executed were clearly not due to exceptional executive action; many parts of government were involved, not least of which the bureaucrats (aka the deep state, those horrible people that actually keep things running).

Exceptional leadership would have been taking action December 2019 or early January - and as many south-east Asian countries show: even clear guidance and simple public health measure matter hugely; but people need to understand and support the measures, because it all hinges on real people changing their behavior; and creating controversy and abusing possible future treatments as distractions from actions that needed to be taken many months ago - and still do - undermines that.

And to cap it all off, the president is not working towards delivering those treatments and vaccines, because he's actively undermining the normal transition of power. Even if the election outcome were uncertain, gambling with people's lives like that shows a careless disregard for actually serving country - because an ethical person would at least work to protect others when it's not only their job, but easy, and conventional to do so.

Coming up with multiple vaccine candidates was fast (it took days to weeks in this case). That's partly because some approaches are straightforward (like growing virus and then inactivating it), partly because there are ready-to-go platforms for vaccine development (e.g., adenovirus-vector and mRNA platforms), and partly because there's been work on closely-related coronaviruses (SARS-CoV-1 and MERS, from which people already knew how to genetically modify the spike protein to remain in its pre-fusion state).

In short, there were several vaccine candidates within days to weeks of the genome being decoded.

What takes time is testing the vaccine candidates for safety and effectiveness. Companies normally go step-by-step. They run a phase-I trial, then evaluate the results and decide whether to go on to a phase-II trial. If they run a phase-II trial, they again wait until the results are in and have been evaluated before moving on to a phase-III trial. That reduces financial risk. In this case, companies began preparing phase-III trials before the phase-II trials were even completed. You can begin enrolling people into the trials and producing the necessary doses before you even know whether the phase-II results are any good. One of the reasons they could do that was because the government was taking on the financial risk.

Technically, Moderna's phase-I trial is not even complete yet: [1]. It runs until November 2021. But Moderna moved forward onto the next phase as soon as it had enough data from the phase-I trial to justify doing so (I assume this meant some combination of safety and efficacy data).

1. https://clinicaltrials.gov/ct2/show/NCT04283461

Wait... it's only in phase 1?

Pfizer is in phase 3 and that's where they test tons of people.

Pfizer is more certain in efficacy.

Moderna is in Phase 3, but they are also in Phase 1, is the point.

Exactly: Moderna's phase-I and phase-III trials are both running right now. [1][2]

1. Phase I: https://clinicaltrials.gov/ct2/show/NCT04283461

2. Phase III: https://clinicaltrials.gov/ct2/show/NCT04470427

Like the old saying, you can have 2 out of 3 of good, fast, cheap. For once, cheap is the option being discarded.

We're even getting it super cheap.

This is already a $10+ trillion pandemic in terms of economic destruction (we'll see economic damage spread out for more than a decade, so the final tally will be even higher). The vaccines are a couple billion dollars each, including manufacturing at scale. A lot of drugs now cost that to bring to market and don't have a small fraction of the positive impact on humanity.

If all that existed were market forces, Moderna and Pfizer could charge ten times what they are. They obviously knew the extreme blowback they'd suffer if they did that (including likely nationalization of their vaccines).

$20-$30 per dose in affluent nations is absurdly cheap to end this nightmare. That's a couple order-out pizzas.

$20 per dose is one hour of work at the median hourly wage. That is several order of magnitude cheaper than the cost so far.

Some, like the AstraZeneca virus, are old vaccines that they never finished developing, taken off the shelf and dusted down. That particular one is a modified SARS vaccine that never made it out of phase two trials, because the market for it disappeared. So by starting from here, they were able to save years of work.

These both use mRNA technology which is new but has heavily been invested in for years. SARS classic, MERS, and Ebola had all spurred development of tools for rapid vaccine development and that meant that a lot of the technical hurdles were accomplished before the crisis started, so the remaining work was still massive but within the range of possibility:

https://www.research.ox.ac.uk/Article/2020-07-19-the-oxford-...

One of the biggest part of the slowdown is communication between private companies which want to bring vaccines to the market and public agencies which want to make sure that it is safe.

To make sure that this is done most effectively, the US government announced "Operation Warp Speed" back in May which has helped private and public organizations work very effectively.

The biggest factor is almost certainly laws in many countries including the US which shield anyone and everyone involved in the making and distribution of a vaccine for COVID (or other pandemics) from any liability whatsoever for any and all consequences of the vaccine. Even if, to take it to the extreme, it kills people and they knew it would kill people and still sold it, they still can't be found liable in any way.

Other comments are correctly pointing out some corollaries of this, such as trials proceeding very quickly and trial phases being run almost in parallel; but the root cause all of this can happen is the legal immunity for the consequences.

The large number of infections is a major factor as well as what everyone else said. If you have a new vaccine for something rare it would be years before you can enough data to say if your vaccine works.

Vaccine technology has been developing rapidly for a couple of decades. Biologists could leverage developments earlier conrona viruses like SARS-1 and MERS. Those were controlled before vaccines were deployed.

The tough nut are retroviruses like HIV. 40 years without a HIV vaccines. Though the related feline virus has a vaccine.

In a crisis things that were previously considered impossible can sometimes get done.

Reply on news.ycombinator.com