Why were Covid vaccine trials so fast? - by Saloni Dattani

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Why were Covid vaccine trials so fast?<br>The timeline to develop coronavirus vaccines blew many predictions out of the water.

Saloni Dattani<br>Jun 26, 2026

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Something I remember fairly vividly from the first few months of the pandemic was a sense of hopelessness that any effective drug or vaccine would become available anytime soon.<br>Most people didn’t believe it was possible to develop vaccines in the timeframe needed for them to be useful. Some looked at past vaccine timelines, which had averaged roughly 8 to 12 years, and thought this one would be similar. Others thought that, even though it was an emergency situation, it would still take at least a year and a half, or two years, or maybe even four.<br>“The grim truth behind this rosy forecast is that a vaccine probably won’t arrive any time soon. Clinical trials almost never succeed. We’ve never released a coronavirus vaccine for humans before. Our record for developing an entirely new vaccine is at least four years.”<br>— Stuart Thompson, New York Times, April 2020.

I had a different conclusion. In a piece I wrote in the summer of 2020, I explained why I believed that vaccines would most likely arrive within a year of the beginning of the pandemic (placing a 58% probability on enough doses for 25 million Americans being approved and available between October 2020 and March 2021, with my central estimate landing around February 2021).<br>We now know how the timeline panned out and my forecast was, if anything, slightly too pessimistic, since vaccines first became available three months earlier, in December 2020. In this post, I want to go into more detail and take a look back at what happened. Why were Covid vaccine trials so fast?

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The scientific foundation

One of the most surprising things about Covid vaccines is how many of them there are: mRNA vaccines (Pfizer and Moderna), viral vector vaccines (Oxford-AstraZeneca and Johnson & Johnson), protein subunit vaccines (Novavax), inactivated whole virus vaccines (Sinovac and Sinopharm), and others. Although their protection dropped as the virus evolved into new strains, I take this bounty of options as a result of the coronavirus being relatively easy to develop vaccines for.<br>Part of the reason is the disease itself. With some infections, like HIV, no one clears the virus naturally or develops lasting immunity to it, so it’s hard to know what a vaccine should mimic. Covid-19 was very different: it was evident early on that most people recovered and developed antibodies that could neutralize the virus. This suggested it was possible to prime the immune system with a vaccine.<br>Another reason was prior research into coronaviruses. Work on SARS and MERS from earlier coronavirus outbreaks meant scientists already understood some of their features. They had identified the key antigen the immune system reacted against – the spike protein – and had animal models and laboratory assays ready to go. Some vaccines against animal coronaviruses had already been developed. Candidate vaccines for the earlier SARS virus had also been developed for humans (and shelved after the 2003 SARS epidemic was contained). When SARS-CoV-2 arrived, lots of this groundwork could be picked up.<br>There’s another feature that explains why some vaccines ended up highly effective: a stabilized spike protein. The spike protein gives the coronavirus its crown-like appearance, and is the main ingredient in most Covid vaccines. But interestingly, it changes shape during an infection. Before it fuses with a cell, it sits in a compact “pre-fusion” form (on the left, below); afterwards, it springs into an elongated “post-fusion” form (on the right). The former boosts immunity most because it’s what antibodies generally encounter, before the virus has entered cells. But when the spike protein is isolated for a vaccine, it tends to collapse into the later, post-fusion form.

Conformation of the pre-fusion (left) vs post-fusion (right) spike protein, as ribbon diagrams. Adapted lightly from Yongfei Cai et al. (2020)<br>Over the past decade, advances in structural biology, especially in cryo-electron microscopy, have helped scientists see the pre-fusion shape of coronaviruses directly. With that knowledge, they introduced a few mutations to stabilize the spike protein in its pre-fusion form, better for the immune system to recognize. This is a big reason why vaccines with the stabilized pre-fusion protein (including the mRNA vaccines and Novavax) generated much stronger neutralizing antibody responses and were likely much more effective than vaccines without the stabilized form (including the AstraZeneca and Sputnik V vaccines).<br>All of these features meant the chances of a vaccine succeeding were somewhat high. They’re also why they could be designed very fast – of course, with a lot of work on the part of scientists. It took two...