Dec 17 2020

It Took Two Days to Develop Moderna’s Vaccine

As the first crop of SARS-CoV-2 vaccines are being rolled out, we can start to see the light at the end of this pandemic tunnel. Still, in the US alone there will probably be another 200,000 deaths before we reach herd immunity. Further, as fast as this vaccine development and deployment was, it’s not clear how much faster it will bring an end to the pandemic. We will likely be 18 months into the pandemic before we have significant vaccine uptake, and that may not be far off from how long the pandemic was going to last in the first place. There is no doubt is will save lives and hasten the end, but still – only after we lost about half a million people to the virus.

The question for the future, therefore, is this – is it possible to develop a vaccine even more quickly? What if we could get a vaccine out, soup to nuts, in just a couple of months. We could have ended the pandemic before it really began. The first shots could have been going out in March, protecting front-line workers and the most vulnerable. This would have dramatically slowed the spread while the general population got the vaccine. By now we would be at the tail end of distribution, not the beginning. The COVID pandemic which disrupted the world would have been more like a mild flu season.

Is this feasible? The answer is a definite yes. In fact, as is now being widely reported, it took Moderna just two days to develop their vaccine. They had the vaccine – in January. This is because Moderna has spent the last 10 years developing the mRNA vaccine technology that they used in their COVID vaccine. This, in fact, is the huge advantage of mRNA vaccines, and partly why this technology was being developed. It worked as designed. As soon as the Chinese government released the genetic sequence of the SARS-CoV-2 virus, that was all Moderna needed. They identified the sequence for the spike protein, plugged that into their vaccine platform, and voila – an mRNA vaccine against the SARS-CoV-2 virus. Actually, I’m sure it was more complex than that, but whatever the technical details, it took only two days. And the core idea here is valid – they really only needed the genetic sequence of the organism, which itself now can be done very quickly.

So what have they been doing for the last 11 months? In short – clinical trials, making sure that the resulting vaccine was in fact safe and effective. The vaccine turned out to be more effective than hoped, about 95% effective in the preliminary analysis of the phase 3 trial. It also appears to be safe, with no serious adverse events in tens of thousands of subjects. They also did need to determine the proper dosing, including that an effective dose would require two administrations about 28 days apart. They had to confirm that the vaccine produced the desired antibodies, that those antibodies neutralized SARS-CoV-2, and then finally that in people it actually protected from the disease. This was all important work, and had to be done.

This research was also done in record speed, because they were allowed to do research in parallel instead of waiting for the full analysis of one stage before progressing to the next. They also started to prep for production before approval, and were given an emergency use authorization. The same is true for Pfizer, although Pfizer and BioNTech funded their own research and development, while Moderna used investors and government grants. All of this was part of Operation Warp Speed, perhaps the one thing that the Trump administration did right during this pandemic. But to give credit where it is properly due – this was not Trump’s idea or initiative. This idea came out of the FDA:

In early April, Peter Marks, an oncologist who has worked in both academia and the drug industry and who heads the FDA division that regulates vaccines, began laying the groundwork for what would become Operation Warp Speed.

The goal of having a vaccine ready by the end of the year was also made possible by 15 years of prior research and regulations. As some are reporting, it was an overnight success story 15 years in the making.

The question now, however, is can we do even better in the future? The idea is to develop a vaccine platform, and test that platform for safety and general efficacy. Then, when a new bug comes along, all you have to do is sequence its genome and then plug that information into the existing platform, and start cranking out vaccines. This literally could be done in a week. Since the platform itself is pre-tested, we won’t need to do months of testing before distribution. Still, we may need to do some testing on the specific vaccine. Perhaps much of this testing can be done with computer modeling, and some with animal testing.

The one thing that will be difficult to determine without extensive clinical trials if efficacy. Even there, we could make some reasonable predictions. We could, theoretically, roll out version 1.0 of the vaccine to the most needy, while tracking the results, and tweaking the formula if necessary. To borrow a saying widely used at the beginning of this pandemic – build the plane while flying it. But in this case, the plane is already 90% built with a known and tested configuration. In hindsight, if we had done this we could have essentially prevented most of the pandemic. The vaccine Moderna had in January turned out to be 95% effective.

The question ultimately comes down to risk vs benefit. We need to get over our evolved but suboptimal instinct to avoid directly causing harm preferentially over passively allowing harm to occur. In the end, the amount of harm is all that matters. In a situation like this, delivering a vaccine as quickly as possible while maintaining sufficient safety and efficacy, there is a sweet spot somewhere that minimizes disease, death, and disruption. We want that sweet spot, even it if means delivering a vaccine that has not been tested as much as we would like. It would mean accepting more risk form the vaccine in order to reduce risk from the pandemic.

The win-win here, however, is that the more we develop a universal vaccine platform, the more we can have the best of both worlds – fast plus safe and effective. But this also means we need public buy in, which requires reassuring the public about the process and the strategy. It also means reassuring the public that the process has not been politicized, and that objective experts are driving (something the TA did poorly).

We need to think carefully about all this, and perhaps evolve Operation Warp Speed into a sustainable vaccine-pandemic strategy. We know another pandemic is coming. We knew this one was coming. Experts were saying for decades that something very much like this was going to happen eventually (just listen to this uncanny interview with infectious disease specialist Mark Crislip from 2007 on the SGU). It’s possible pandemics are going to be more frequent, with global travel, trade, and populations what they are. We need a strategy to deal with them while they are just starting. Choose your metaphor here – you don’t wait to build a fire department until after the fire is raging.

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