Surprising conflicts and collaborations built the coronavirus vaccines
It took 11 months to go from the first genetic sequence of the pandemic coronavirus to vaccines that could stop infections. Some of these vaccines have used traditional approaches, such as fragments of the virus that could stimulate an immune response. Others, called mRNA vaccines, have used new technology to make the body’s own cells make these virus fragments. The fire has now reached hundreds of millions of weapons and has shown remarkable effectiveness.
But those 11 months have been frantic and involved a complex and often heavy combination of quiet scientists, big pharmaceutical companies, regulatory agencies and, in the United States, a White House desperate to show progress against COVID. In a book published today, The first shots (Mariner Books) reporter Brendan Borrell goes behind the scenes to show how these different and often competing forces came together to make vaccines in record time. He spoke to 150 people involved in the effort and learned about the first scientific breakthroughs, the arguments about the best ways to test new vaccines, and how the U.S. government supported the grand vaccination campaign. Borrell spoke with American scientist on these challenges.
[An edited transcript of the interview follows.]
Companies such as Pfizer and Moderna get a lot of credit for vaccines. But didn’t you discover that much of the revolutionary work began in academic and government labs?
Yes. A few years ago, Barney graham, deputy director of the Vaccine Research Center at the National Institutes of Health, worked on respiratory syncytial virus, which affects infants and the elderly, and it was his real passion. Jason mclellan, a structural biologist, worked with him on viral proteins. These viruses have proteins on their surface, spike proteins, or something similar, that allow them to attach to cells. These proteins change shape, which is a problem for your immune system. McClellan and Graham came up with a strategy to produce spikes that would get stuck in a position, much like a dummy, that your body can learn to attack them.
Jason went to work at the University of Texas, and then when this new coronavirus broke, Barney called and sort of said, “Hey, let’s get the group back together.” As soon as the virus sequence was published online on January 10, McLellan’s lab began examining the spike protein by cryomicroscopy and obtained an image when it was stuck in this vulnerable position. And it made them feel that their vaccine strategy was going to work. And Moderna, who had partnered with NIH, used the design and built an mRNA vaccine around it. Moderna has since said that they independently came up with a similar design.
And that was before anyone had a lot of data that the strategy was going to work, right?
Yes, and it is there Kizzy corbett, an immunologist who was in Graham’s lab, became an extremely important scientist. Everyone was rushing to develop these cutting edge proteins, and Moderna was rushing to turn them into vaccines, and they needed animal data to show that they worked and what the right dose was. So they get maybe a shipment of 400 mice, and they have to come down and vaccinate them all, until their fingers are sore, and produce this torrent of papers.
But her public profile went beyond what she did in the lab. She’s a black woman who grew up in a small town in North Carolina. She’s got that Twitter personality, and she’s started spreading the word about vaccine safety and reducing hesitation in the black community, where there had been medical parodies in the past. As they embarked on subsequent trials, Corbett would go out and lecture, trying to get the word out that, hey, this was done by black scientists and we did it right.
How did this effort turn into Operation Warp Speed? The Trump administration was generally against government assistance to big business. Yet here they have offered billions of dollars and other aids.
There is a great irony here. There was a crisis around the period of April 2020 [as the virus was spreading]. Moderna was making investments, but other drug companies were saying that in order to do it profitably, we can’t just put all of our money into this vaccine. So things were moving slowly. And if you go back to that time, even scientists like Anthony Fauci and Deborah Birx from the White House Coronavirus Task Force say, hey, if we keep the social distancing measures going, we might not have not another peak of the virus, maybe it will come back in winter. Yet parts of the Trump administration began to reject the country’s closure and wanted to reopen. So these public health measures would no longer work. And a vaccine was sort of the only option we had left.
What drove vaccine development into high gear?
The administration wanted a quick fix, so the pressure was mounting. Robert Kadlec, assistant secretary for preparedness and response at the US Department of Health and Human Services, and Peter Marks, director of the Center for Biologics Evaluation and Research at the FDA, wanted to invest more money in vaccines, and they have seen this opening. The same goes for Health Secretary Alex Azar, who has essentially been kicked out of the coronavirus task force. But now he had the chance to bring Operation Warp Speed to the administration and sell it to them. It was a confluence of factors.
But not everyone agreed on how to test these vaccines on people, right?
As things were falling into place in the spring of 2020, there was quite a standoff. One of the first problems was that Peter Marks wanted to run what is called a master protocol. The idea was that all candidate vaccines would be compared face to face with a single placebo group. Then you could say “this vaccine is the best in the whole country, we should spend all our money on this one.” But some NIH members felt that if you did a big trial but a safety issue emerged with a vaccine, then the whole trial would stop. So they wanted to have semi-independent trials. If a vaccine had a problem, it wouldn’t delay it. They called these trials harmonized. The tests would have roughly the same rules, the same protocol and would be performed on different but comparable groups of people. It has become the compromise.
Was it difficult to involve a variety of people in these trials?
It has become another difficult problem. When Moderna began clinical trials, the representation of blacks and Hispanics was perhaps half of what it is in the general American population. Yet one of the cases presented by the NIH was that COVID had not hit the nation in the same way. It hit black communities harder. So they wanted the trials to be more inclusive. (Pfizer didn’t have as much of a lack of diversity in their essay as it was taller and had a big international footprint, so they had different types of people.)
But Moderna and the people in charge of Operation Warp Speed wanted to recruit people quickly because it was a crisis. They were using commercial clinical trial sites that were able to recruit people quickly. [But these operations did not emphasize diversity.] The NIH, however, used to involve local communities through more academic sites. These sites were, however, slower. But the NIH point of view was that it would be a better and more representative trial if these sites were involved. They have embarked on a lobbying campaign, with some bigwigs fundamentally shaming the company on this point. Ultimately, they won this battle.
Young children, however, were not in the initial trials. Why not? Today, the FDA plans to authorize the Pfizer vaccine for children between the ages of 5 and 11.
For Operation Warp Speed, involving children in the trials was not an initial concern. They were more worried about the elderly who were getting really sick. And the thing with kids is that they’re not little adults. Their immune systems are different. So you have to be very careful when going down the age range. You run all the basic assay experiments again. The FDA decided to slow the approval of children’s vaccines because it wanted six months of safety data instead of two months. It’s definitely a day that many parents have been waiting for.