Kathleen Neuzil, Larry Corey
Co-Principal Investigators in Vaccines, the COVID-19 Prevention Trials Network
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, may be the face of a coordinated U.S. effort to find effective ways to shield against COVID-19 infection, but two renowned virologists have those boots on the ground.
In July, the NIH unveiled the COVID-19 Prevention Trials Network (CoVPN) to conduct large-scale phase 3 prevention trials for several vaccines and monoclonal antibodies. Larry Corey of the Fred Hutchinson Cancer Research Center and Kathleen Neuzil of the University of Maryland School of Medicine took the reins as co-principal investigators for the network’s vaccine tests.
In short, they’re leading a major effort—now comprising shots from AstraZeneca, Johnson & Johnson, Moderna and Pfizer/BioNTech—to determine whether the U.S. will have an effective COVID vaccine.
The genesis of CoVPN
CoVPN combines four NIAID-funded clinical trials networks, the Fred Hutch-based HIV Vaccine Trials Network (HVTN) among them. Corey has led that network since 1999, and to him, it was a perfect platform for CoVPN to use as its center. “We have worked for over 20 years in establishing clinical trial programs [and] have laboratories that can be used to uniformly evaluate vaccines,” he said.
Corey had been working with Fauci, a longtime friend, on the idea of an overarching vaccine trials effort since March. Drug companies are fully capable of funding and running their own trials, but industry watchers and drugmakers often disagree about how to compare data from multiple clinical tests—or whether to compare it at all.
“Eventually there may be different results between different vaccine platforms, and the issue is, is that because the trials were done differently, the assays are different, or because the population are different, or is it because there’s really truth in the differences between the platforms,” Corey explained.
So, alongside Fauci, NIH Director Francis Collins and NIAID Vaccine Research Center chief John Mascola, Corey backed a “harmonized” approach to COVID vaccine R&D in a Science article in May. During a public health emergency, they argued, a trial organization with shared independent laboratories and common data and safety monitoring board would help regulators and the public “make objective assessment” of how the various vaccines stack up against one another.
Now, CoVPN allows for a common way to compare immune responses among the various vaccines in development, because the trial designs, the sampling, and the way trial participants are followed are very similar, he said.
Weekend meetings, little sleep
Meanwhile, Neuzil is no stranger to collaborative research herself. Considered one of the most influential scientists in vaccine development, Neuzil serves as co-principal investigator of the Infectious Diseases Clinical Research Consortium, which the NIAID launched right before the pandemic to foster collaborative research in diseases it considers priorities. It’s one of the four networks now part of CoVPN.
Neuzil’s previous work covers many respiratory pathogens, including pandemic influenza. To her, the types of vaccines CoVPN is testing are familiar, but the virus is not. “We have decades of experience using influenza in vaccines and know a lot about immunity, natural history, vaccine responses when it comes to vaccinating against different flu strains,” she said. “In the case of the novel coronavirus, we were designing vaccine trials … at the same time as we were learning about the new virus.”
The vaccine portion of CoVPN currently encompasses four active studies: the Ensemble trial of Johnson & Johnson’s Ad26.COV2.S, AstraZeneca’s trial of AZD1222, Moderna’s COVE study of its mRNA shot mRNA-1273, and one for Pfizer and BioNTech’s BNT162b2. Together, they’re aiming to enroll over 160,000 volunteers, and they’ve attracted tens of thousands already.
So many things can go wrong in large vaccine trials, including manufacturing delays and safety-related pauses—as AstraZeneca and J&J know. Corey and Neuzil tackle these problems; they make sure trial protocols are followed and coordinate the action to make sure all stakeholders stay updated.
The job comes with an unprecedented sense of urgency or, by Neuzil’s words, “stress from the pressure to accelerate the availability of countermeasures.” For both Corey and Neuzil, it involves sleep deprivation and no weekends, because Saturdays and Sundays are “often the only time we can get busy people together for teleconferences and check-ins,” Neuzil said. Though located in Seattle, Corey’s been running on East Coast time, up at 5:00 in the morning and to bed after midnight, seven days a week.
The job requires frequent phone calls and teleconferences to coordinate with the U.S. government's Operation Warp Speed, with the biopharma companies involved in the trials and the scientists executing them. A lot of the confabs are what Corey described as “thinking calls” about both specific operations and big-picture strategies.
One type of pressure that hasn't been a factor? Political pressure, Corey and Neuzil said, even as President Donald Trump very publicly pushed for a shot by election day.
Focusing on the job at hand is why, Corey said. “The pressure for me has always been building the enterprise that actually conducts the trials, and then getting them going and making sure that they’re well-designed, and that they appear to be on course to answer the question of whether a vaccine works or not, in whom and how well,” he said. “I feel all of that is being accomplished.”
For her part, Neuzil said the people involved aren't the type to let politics get in the way. “We have the best science behind these trials and the best people conducting these trials,” she said. “We have an independent, highly qualified and expert data and safety monitoring board for our clinical trials and the best regulatory agency in the world reviewing the safety and the data from these trials. So, yes, I am confident the system is working without political interference.”
All three vaccine candidates in CoVPN have shown in early-phase trials that they could induce strong antibody responses. But one major uncertainty hanging over everybody’s head is whether the antibodies can indeed protect against SARS-CoV-2 infection, or at least reduce the risk of COVID-related respiratory disease when a person is infected.
That’s what Corey, Neuzil and the CoVPN team aim to find out from the phase 3 trials. Nothing is yet certain. But they're “getting more optimistic,” given that monoclonal antibodies against the coronavirus’ spike protein—which the vaccines are also based on—have shown some efficacy. Their antiviral effects suggest that “the spike protein is a potent immunogen, and it’s an appropriate target for a vaccine,” Corey said.
Of course, we will only know for sure when the studies read out, which begs the next burning question: When? As the trials’ leaders, Corey and Neuzil agree that an emergency use authorization by the end of the year is possible, just as many experts, including Fauci, have suggested.
“We knew that to meet that timeline, everything had to go right,” Neuzil said. “We needed strong leadership, a focus on a common goal, and the resources to execute the plan.”
Looking toward the next pandemic, Corey and Neuzil said the investments in science and technology, as well as the concerted effort by the scientific community, to fight COVID are getting the world ready for future outbreaks, too.
“We are definitely more prepared now for any future pandemic,” Neuzil said. “The key will be to sustain many of these efforts. We must continue to invest in basic science and in better public health infrastructure and community outreach.”
But the fact that we still don’t have a vaccine for HIV after 40 years is reason for caution. “Building scientific infrastructure to handle pandemics is a good idea,” Corey said. “Whether that will solve the next one, a lot of that is pathogen-specific.”