• Wed. Dec 1st, 2021

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Surprising Conflicts and Collaborations Built the Coronavirus Vaccines

It took 11 months to get from the first genetic sequence of the pandemic-causing coronavirus to vaccines that could stop infections. Some of those vaccines used traditional approaches, such as fragments of the virus that could stimulate an immune response. Others, called mRNA vaccines, used new technology to get the body’s own cells to make those virus fragments. The shots have now gone into hundreds of millions of arms and have shown remarkable effectiveness.

But those 11 months were frantic, and involved a complex and often fraught combination of low-profile scientists, big drug companies, regulatory agencies, and—in the U.S.—a White House desperate to show progress against COVID. In a  book published today, The First Shots (Mariner Books), journalist 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 initial scientific breakthroughs, arguments about the best ways to test the new vaccines, and how the U.S. government got behind the big vaccine push. Borrell talked with Scientific American about these challenges.

[An edited transcript of the interview follows.]

Companies such as Pfizer and Moderna are getting lots of credit for vaccines. But didn’t you find that a lot of the groundbreaking work started in university and government labs?

Yes. Several years ago, Barney Graham, deputy director of the Vaccine Research Center at the National Institutes of Health, was working on respiratory syncytial virus, which affects infants and the elderly, and it was his real passion. Jason McLellan, a structural biologist, was working with him on the viral proteins. These viruses have proteins on their surfaces, 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 be stuck in one position, kind of like a mannequin, that that your body can learn to attack them.

Jason went off to work at University of Texas, and then when this new coronavirus broke out Barney called and kind of said “Hey, lets get the band together again.” As soon as the virus’s sequence was published online on January 10, McLellan’s lab started examining the spike protein with electron cryomicroscopy, and got an image when it was stuck in that one vulnerable position. And that gave them a sense their vaccine strategy was going to work. And Moderna, which had been partnering with NIH, used the design and built an mRNA vaccine around it. Moderna has since said they independently came up with a similar design.

And this was before anyone had much data indicating the strategy was going to work, right?

Yes, and that’s where Kizzy Corbett, an immunologist who was in Graham’s lab, became a hugely important scientist. Everyone was racing to develop these spike proteins, and Moderna was racing to make them into vaccines, and they needed animal data to show they worked and what a good dose was. So, they get maybe a shipment of 400 mice, and they have to go down and vaccinate all of them, until their fingers were sore, and churn out this torrent of papers.

But her public profile went beyond what she was doing in the lab. She’s a Black woman who grow up in a small town in North Carolina. She has this Twitter personality, and she started spreading the word about vaccine safety and reducing hesitancy in the Black community, where there were medical travesties in the past. As they were going into later trials, Corbett was getting out and giving talks, trying to spread the word that, hey, this was made by Black scientists and we did this right.

How did this effort turn into Operation Warp Speed? The Trump administration was generally against government aid to big businesses. Yet here they offered billions of dollars and other help.

There is a great irony there. There was a crisis around the April 2020 time period [as the virus was spreading]. Moderna was making some investments, but other drugmakers were saying that to do this in a profitable way we can’t just throw all of our money into this vaccine. So, things were moving slowly. And if you rewind to that time period, even scientists such as Anthony Fauci and Deborah Birx on the White House coronavirus task force are saying, hey, if we keep up social distancing measures, maybe we’re not going to have another peak of the virus, maybe it’ll come back in the winter. Yet elements of the Trump administration started to reject the closing of the country and wanted to reopen. So, these public health measures were no longer going to work. And a vaccine was kind of the only option that we had left.

What pushed vaccine development into a higher gear?

The administration wanted a quick fix, so the pressure was building. Robert Kadlec, the assistant secretary for preparedness and response at the U.S. Department of Health and Human Services, and Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, wanted to put more money into vaccines, and they saw this opening. So did the health secretary, Alex Azar, who had basically been forced 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 those vaccines on people, right?

As things were coming together in the spring of 2020, there was quite a tug of war. One of the first issues was that Peter Marks had wanted to run what’s called a master protocol. The idea was that all the vaccine candidates would be compared head-to-head against a single placebo group. Then you’d be able to say “this vaccine is the best ever in the whole country, we should spend all of our money on this one.” But some of the folks at NIH felt that that if you did one big trial but a safety problem emerged with one vaccine, then the whole trial would come to halt. So, they wanted to have semi-independent trials. If one vaccine had an issue it wouldn’t hold the whole thing up. They called these harmonized trials. The tests would have approximately the same rules, the same protocol, and be on different yet comparable groups of people. That became the compromise.

Was it hard to get a diversity of people into those trials?

That became another hard issue. When Moderna first started their clinical trials, the representation of Black people and Hispanic people was perhaps half what it is in the overall U.S. population. Yet one of the cases that NIH made was that COVID had not struck the nation equally. It affected Black communities more severely. So, they wanted the trials to be more inclusive. (Pfizer did not have as much of a diversity shortfall in their trial because it was larger and had a big international footprint, so they got different types of people.)

But Moderna, and officials in Operation Warp Speed, wanted to recruit people quickly because this was a crisis. They were using commercial clinical trial sites that were good at recruiting people fast. [But these operations did not emphasize diversity.] NIH, though, had a history of involving local communities through more academic sites. Those sites were slower, however. But NIH’s point was that it would be a better, more representative trial if those sites were involved. They embarked on a pressure campaign, with some bigwigs basically shaming the company on this point. Eventually they won that battle.

Young children, however, were not in the initial trials. Why not? Today the FDA is considering authorizing the Pfizer vaccine for children aged five through 11.

For Operation Warp Speed, getting kids into the trials was not an initial concern. They were more worried about the elderly who were getting really ill. And the thing about children is that they are not small adults. Their immune systems are different. So you have to be very careful as you move down the age range. You run all the basic dosing experiments again. The FDA decided to slow down the approval of the childhood vaccines because they wanted six months of safety data instead of two months. This is definitely a day lots of parents have been waiting for.