National Institute of Allergy and Infectious Diseases/National Institutes of Health
Science’s COVID-19 reporting is supported by the Pulitzer Center.
The crowded race to develop a vaccine against the new coronavirus just received a potential billion-dollar boost: Johnson & Johnson (J&J) announced on 30 March that it and the U.S. government, through a military research agency, would together devote up to that amount to move a candidate product made by its Janssen division across the finish line.
Janssen’s vaccine is built around an engineered version of adenovirus 26 (Ad26), which normally causes common colds but has been disabled so that it cannot replicate. Company scientists stich into this Ad26 “vector” a gene for the surface protein from the new coronavirus spreading around the world. Janssen is testing this same Ad26 platform in vaccines against Ebola, HIV, respiratory syncytial virus, and Zika. J&J had $42 billion in pharmaceutical sales last year, making it the sixth largest big pharma company. Sanofi is the only other in the top 10 that has a COVID-19 vaccine project.
Florian Krammer, a researcher at the Icahn School of Medicine at Mount Sinai, who has co-authored a status report in Immunity about the COVID-19 vaccine field, says “it’s great” that a big pharma company like this has committed so much to the project, but he cautions against banking on any one effort. “The more the merrier—and I hope they’re successful—but the question is really whether they have an advantage over anyone else,” Krammer says.
Paul Stoffels, J&J’s chief scientific officer and a veteran HIV drug developer, spoke with Science yesterday from his home in Belgium, where he, like many others around the world trying to slow the spread of the coronavirus, is sheltered in place. He says the effort will be nonprofit and the vaccine will be accessible to all through some global mechanism still to be determined. “We’re not going to decide who will get the vaccine, because that’s not up to us. This has never happened before, so we have to invent something on how to do this,” he says. This interview had been edited for brevity and clarity.
Q: The U.S. government, through the Biomedical Advanced Research and Development Authority (BARDA) has committed $456 million to the Janssen effort and the company says it will commit roughly an equal amount. Will BARDA be doling out the money in installments if you meet milestones?
A: We’re jointly investing in the R&D part of this, and that will bring us, hopefully, to approval. And then in parallel, we’re investing more in the manufacturing, so we are creating additional capacity. Of course, it’s step by step—it has to work—but there’s no hesitation now to do everything in parallel. When we have clinical data, we will have the capacity to scale up to very large quantities. That is the short and long story.
Q: What is your vaccine and what’s the strategy?
A: We have the Ad26 vector. We have made 10 different constructs and tested them all in mice, and we took the most immunogenic one. And then in parallel, we looked at the upscaling in this cell line that allows us to grow the cells at very high density and have a huge output. That gives us up to 300 million vaccines per 2000-liter vessel per year.
We learned from what we did in Zika that with the right [Ad26] vector, we can get very significant immunity. Here we need to get to good protection on a very large scale for a much less lethal disease. We can do it with one dose, but we’re going to test two doses in the clinic. In a crisis situation we probably can do with one dose and a boost 1 year later to up the immunity.
Q: What’s your capacity to produce vaccine for the world?
A: We can make 300 million vaccines, in a 2000-liter vessel, on an annual basis. We have one fully functioning facility now with a 2000-liter vessel, and we’re starting to set up the second one in the U.S. that will be ready by the end of the year. We’re talking to the vaccine companies in other parts of the world who have similar capabilities to see which ones we will bring on board as partners—or we might still consider doing something ourselves. We think we need to get to 1 billion doses, so we need four plants. And if we need more, we’ll adjust to bring more on board.
Q: Have you vaccinated monkeys yet with your COVID-19 vaccine and then intentionally attempted to infect them with the virus to see whether they’re protected?
A: That is the next step now. We are working with Dan Barouch at Harvard [University], and three animals are being vaccinated as we speak.
Q: Why will it take until September to launch a phase I clinical trial when others have aggressively moved to the clinic more quickly?
A: With vectors like Ad26, you need to get the seeds [copies of the engineered virus] to do biological manufacturing. That takes time to make sure we select the right clones and that we have a stable selection so we can grow the right ones. We grow them up so that we have the seeds for the next years to come to produce thousands of hundreds of batches.
Q: With adenovirus vectors, there’s a concern that if the viruses have spread widely in populations, many people will have immune responses to them that will knock out the vector and undermine the vaccine. Is there immunity in the population to Ad26?
A: We’ve tested that extensively and it’s very limited. We selected Ad26 based on its nonpresence in humans—as well as the fact that it’s a nonreplicating vector, which is very important for the safety. We have 50,000 people so far in the vaccine projects against different diseases who have received our Ad26-based vaccines and we have a very, very solid safety profile.
Janssen Vaccines and Prevention BV, Leiden, NL
Q: Which immune responses were most important to you when selecting your most promising COVID-19 vaccine candidate?
A: At the moment, the selection criteria is neutralizing antibodies. [In test tube experiments, these antibodies can “neutralize” the ability of the virus to infect cells.]
Q: If you start phase I trials in September, what’s your plan for moving forward?
A: Because we have a lot of safety data, we can accelerate the timeline from a phase I [trial of safety and immune responses] to a proof-of-concept study. We are used to recruiting extremely fast, so we could do 250, 500 people in a day and 1 month later, 3 days after the blood is taken, we should be able to know the result.
Q: So you want to do a phase II efficacy study in 500 people as a proof-of-concept trial?
A: I’m talking about thousands of people in an emergency use application to get to a large enough phase II study in the real world. That could be done very quickly, but you have to be in an epidemic zone, and it’s not clear in the second half of the year where that will be. Almost surely it will be an epidemic somewhere in the world.
Q: How long does it take you to get those phase I data that would allow you to launch this large phase II study?
A: We have been working like crazy to get to this point, 10 weeks after the start of the vaccine project. We have 4000 people in clinical research all over the world and we have the capability to recruit a very large study in very a short time. Six weeks.
Q: So if this virus indeed has a seasonal signature, and it does return in the Northern Hemisphere in the temperate regions in the fall, early winter, you could have a vaccine ready for that large trial in that time frame?
A: That’s the idea.
Q: Let’s say it works. What about accessibility? If you make 1 billion doses how do people around the world, in rich and poor countries, divide up who gets your vaccine?
A: First of all, getting to a billion doses is trying to avoid a war about vaccines—there will be enough vaccine in the world to get going. But we’ll work with the health authorities. We are going to do this on a not-for-profit basis. This is the one time in history that we can really do something for the world that is really transformational. And then everyone can partner with us because we’re on equal footing. That’s why I hope we can scale up much faster, working with governments all over the world. I’m almost sure that it will accelerate everything by 6 months because we’re doing it not-for-profit. This is one of the biggest, if not the biggest, initiatives in J&J history to try and make a difference for the world.
Source: Science Mag