The precision and speed of COVID-19 vaccine development was made possible by recent R&D advancements and a strengthened network of public-private partnerships, NIH National Institute for Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VCR) Deputy Director Barney Graham affirmed in his keynote presentation at the opening session of the CASSS Well-Characterized Biotechnology Products (WCBP) conference in late January.
Building on the foundation of these more robust technologies and partnerships, he explained, “we ended up with a good result – even better than we had hoped.”
The COVID experience and learnings, in turn, Graham emphasized, suggest that “prototype pathogen preparedness is feasible, even for the other viral families that remain out there” where vaccine development has not yet matured.
In his keynote presentation and the Q&A that followed, Graham shared a wealth of insights on how the accelerated COVID-19 vaccine development was made possible by the recent science and technology advances and on the role that the NIAID’s VCR, in collaboration with a network of partners, played in empowering the process – a role that Graham was intimately engaged in as a global leader in vaccine research.
In reviewing the rapidly evolving vaccine R&D landscape, he explained how, in the past, viruses “really have had the advantage over us, because they can adapt faster and have more mechanisms to adapt than we have ever had with our approaches to contact tracing and quarantine.”
However, the advantage has been shifting in favor of the technologies over the viruses, he affirmed. “I think we are in an era where we could apply them in a way that makes this very historically uncertain process of biological development more of an engineering kind of exercise.”
Structure-based design and some of the new approaches to protein engineering and self-assembling nanoparticles, he stressed, can not only make this approach more precise and predicable, but also more rapid. “And combining precision and speed is what we need in order to address emerging infectious diseases that we have faced over this last decade.” [See IPQ August 27, 2020 for more insights on this shift in the product development paradigm from discovery to design and its implications by American Gene Technologies CEO Jeff Galvin.]
Graham then reviewed the human virus landscape – explaining how the problem is a finite one that now lends itself to taking a systematic, proactive approach to understanding the structures and replication pathways needed to develop vaccines, as well as antivirals and other countermeasures, and establishing a “prototype pathogen approach to pandemic preparedness.”
The labor, he proposed, could be divided between pathogen specialists, supported by systems and groups, that could perform and consolidate the core research specific to the pathogen class.
NIAID’s Vaccine Research Center Plays Coordinating Role in Vaccine R&D
Graham went on to explain how his Vaccine Research Center (VRC) at NIAID, founded in 2000 originally to focus on HIV vaccine development, has proceeded to play this kind of coordinating role.
He reviewed the efforts and learnings of the VRC in responding to viruses such as Ebola and Zika – stressing how critical it is to match the rapidly evolving outbreak situations with the speed of research to facilitate bringing development projects to fruition.
One of the learnings on the virus and protein structures over the past decade was how potent the mRNA delivery approach could be for vaccine antigens. Engagement with Moderna on the research during the 2016 Zika outbreak led to further collaboration with the company to demonstrate the feasibility of applying an mRNA prototype approach on both paramyxoviruses and coronaviruses.
Graham then took the audience through the COVID-19 vaccine development story that unfolded with the emergence of the SARS-2 coronavirus in early 2020 – beginning with a thought-provoking look at the previous major global pandemics and the current vaccine landscape.
He reviewed the highlights along the COVID vaccine development timeline and how the past science and technology components of the puzzle were brought to bear in the more than 200 vaccine projects launched – over 60 of which have reached the clinical testing stage, with a hand-full of very viable vaccines available for use by year’s end.
Funding Allows Shift from Sequential to Parallel Development Processes
Graham’s highly engaging insights continued to flow during the Q&A that followed his presentation, which was moderated by conference chair Julia Edwards, who is Pharma Technical Regulatory Global Head, Biologics Marketed Products for Genentech.
He explained that while close collaboration between scientists and regulatory experts through the process was a critical element, what really made it feasible to compress the animal studies and clinical timelines was the influx of financial resources.
“The ability for the companies to make decisions that were all happening in parallel and not sequentially is what allowed them to go fast,” Graham said. When not wanting to put resources unnecessarily at risk, “you do things serially.” The parallel development allowed the safety steps to also be done on the accelerated timelines.
While the COVID experience has “at least changed some of the paradigms and ways of thinking about what is possible” for acceleration in the face of a global crisis of this proportion, Graham cautions that there will not “always be billions of dollars provided ahead of time at risk, not knowing whether any of these things would work.”
HIV Vaccine Absence and Handling COVID Variants Addressed
The second question put forward from the audience was why a vaccine for HIV has not yet been developed.
Graham explained that the number of ways the virus has for immune evasion is among the complexities involved. “Hopefully,” he said, “as we learn more about each of these other, simpler viruses, we may take all that and apply it back together against HIV, and eventually have a solution, but it is really not easy.”
Asked to comment on vaccine strategies that might be more efficient against new coronavirus variants, Graham explained the issues involved. He noted that the mRNA technology probably offers the fastest manufacturing pathway, and cautioned that there will be some challenges for regulatory decision makers around how much information is needed to support making switches.
Edwards posed a follow-up question on whether different sequences from different variants could be combined in one vaccine to reduce the risk of escaped mutations.
Graham pointed out that “as long as we have vaccines that have a lot of antigenic content that are inducing antibodies to a lot of surfaces and parts of the different spike proteins, we have a chance of having immune responses that can resist evasion or escape. So the question is just when is there too much change that forces you to change vaccines. I do not think we are there yet, but we may get there over the course of the next few years.”
Vaccine Education Is a Key NIAID Priority
Asked about addressing vaccine hesitancy in the general population, Graham emphasized the engagement and commitment of the leadership at NIAID in community education to help increase the understanding about how the COVID vaccines are being made and why they can be trusted.
“Maybe we have an opportunity during this crisis that all of us are experiencing together to make changes in the way people think about vaccines in general and the way they might trust,” he said. “We may be able to gain a little bit of trust back in the federal government and the biomedical research enterprise, and hopefully we can turn that needle back a little bit more toward the trust. So there is a lot of effort being put into this.”
The goal is better informed decision-making, Graham said, clearly articulating the stakes of the decision.
“Everybody is going to be immune in a few years, and you are either going to get that way by infection or by vaccination. The infection gives you a one or two percent chance of dying. The immunization is giving you a couple of chances out of a million to have an allergic reaction. So I think people have to decide which one is the safest.”