iBio's Melissa Berquist on Next-Gen Vaccines and Adapting to COVID-19 as an Endemic Disease
With the number of COVID-19 cases increasing globally, prompting more viral mutations and, consequently, new variants, it’s becoming more apparent that COVID-19 will be with us long-term.?Melissa Berquist, Ph.D., iBio's Vice President and Head of Vaccines and Animal Health, shares her take on emerging variants, iBio's vaccine development, adapting to COVID-19 as an endemic disease, and the World Vaccine Conference in Barcelona.?
Q. A growing number of scientists and epidemiologists see COVID-19 becoming endemic, much like the flu. How should government and industry adapt??
A. While a COVID-19 endemic will likely evolve, I don’t believe we have reached that point. We are still grappling with Omicron, the inevitable evolution of emerging variants, and waning immunity with first-generation vaccines focused on the variable spike protein. Opinions vary on endemicity, but we know that this virus is prolific and that its mutations have made it difficult to predict with any meaningful precision. We've identified SARS-CoV-2 in deer, mink, rodents, domestic cats and dogs, lions, tigers, and humans. It's likely here to stay. What’s critical now is managing this transition to an endemic and being prepared for something that could look very much like – or very different from - the flu. ?
Even if COVID-19 becomes endemic, it could continue to result in significant annual deaths and illnesses. Initial vaccine development efforts to fight the pandemic were laudable and, by most accounts, successful. Vaccines were produced in record time, with efficacy exceeding expectations in preventing severe disease and death. Our rapid response worked very well as a short-term means to staunch the pandemic in places where vaccines have been broadly distributed and enabled our healthcare systems to catch up in terms of available treatment options. Still, we have seen the challenges with distribution, durability, and access of vaccines; combined with the mutability in escaping the protection they provide, it’s clear that opportunities remain to strengthen our existing vaccine strategies. ?
The time is now for us to shift focus to the next generation of vaccines that address the gaps in existing technologies so that we can adapt to the future endemic. There's a tremendous opportunity for better collaboration across sectors - government, industry, academia, and non-profit - to accelerate this work. To spur innovation, governments should prioritize funding of efforts that don't merely replicate past successes, but instead, invest behind broader coverage, more accessible vaccines that have the potential to overcome remaining obstacles for our global population. As we know and have experienced, this virus won't be contained anywhere until we contain it everywhere.?
Q. Why is iBio still pursuing a COVID-19 vaccine, and what is its strategy??
A. Existing vaccines don’t stop transmission of SARS-CoV-2, and they do not fully address the challenges of accessibility, durability, and – importantly - new variants, as omicron’s evolutionary success is proving right now.?It’s probable that omicron won’t be the last variant in which significant spike protein mutations enable the virus to skirt existing defenses. As the WHO recently suggested, “a vaccination strategy based on repeated booster doses of the original vaccine composition is unlikely to be appropriate or sustainable.” So, we believe that second-generation vaccines will be needed to contain the pandemic and manage public health as COVID-19 becomes endemic, and our vaccine candidate, IBIO-202, fits this definition. ?
Over the past year, substantial research has supported the need for new alternatives to current vaccines that target only the frequently changing spike (S) protein.?One solution includes generating more durable immunity by targeting a small part of a less mutable protein that sits inside the virus, such as the nucelocapsid (N) protein. This protein is more highly conserved within SARS-CoV-2, and?some studies suggest that the N protein might be a key to a pan-coronavirus vaccine.?For instance, a recent study by researchers at Imperial College London found that memory T-cells generated from the N-, not the S-, protein from some coronaviruses provide cross-protection against other coronaviruses. Meanwhile, other studies observed that N-directed vaccines may also provide better protection against the neurological effects of COVID-19 than just S-directed immunity. Additionally, The N protein is expressed abundantly, resulting in an immune response during natural infection. All of this supports the design of our next-generation COVID vaccine, IBIO-202, which targets the N protein. Our early research indicates that IBIO-202 generates both humoral (antibody) and cellular (memory T-cell) immune responses, making it more likely to protect against emerging variants and offer longer-lasting immunity.?The potential for durable immunity combined with the track record of safety and success of recombinant protein vaccines suggests that IBIO-202 is a strong candidate and may fill existing gaps. ?
It also may address some of the significant barriers to global access, specifically concerning cold-chain storage and even cost. Delivering vaccines by means other than intramuscular injection could expand access, too, and IBIO-202 could play a role there as we evaluate alternate delivery strategies. Our plant-based FastPharming? System also ensures rapid scalability.?
Q. The World Vaccine Congress in Europe brought together leading global vaccine makers, including many that have developed or are developing COVID-19 vaccines. What did you learn??
One thing that I heard during the keynote panel from experts from a variety of companies, including GSK's global head of vaccines, is that recombinant-protein-based technology may be well suited to mix-and-match booster strategies. We know that they are exponentially safe, irrespective of expression platform, and they induce an immunogenic response to antigenic targets. They work very well.?
To me, it felt like someone else was validating the approach that we're taking with IBIO-202 as a heterologous booster approach, meaning we intend for it to complement existing S-directed vaccines since such a large proportion of the U.S. population is already vaccinated and global numbers are catching up where nearly two-thirds of all individuals have received at least one dose. Those numbers, combined with huge numbers of global infections over the past 2-years, mean there are increasingly fewer truly na?ve individuals. We have an opportunity to induce a more durable immune response while leveraging the initial, shorter-term protection that spike-based immunity may provide.?How can we improve durability with an N-directed approach? How can we cement the body's immune response??
There was interesting data presented on the differing immune responses in convalescent patients as correlated to severity of COVID-19, the disease caused by SARS-CoV-2 infection. Much of the data examines the role of the nucleocapsid protein in the body's immunogenic response for clearing the virus. A paper was presented that demonstrates how T-cell receptor stimulation and differentiation from an effector T-cell to a memory T-cell is driven by some specific transcriptomic signatures. The body is micro-regulating the environment in terms of making this switch in between two different types of T-cells. The memory T-cell needs to be re-activated when the body sees a pathogenic agent for the second time, sometime in the future. The authors looked at two different N-directed lines that were driving this transcriptomic change, and both of those signatures are part of the IBIO-202 antigen. Overall, the benefits of both our recombinant protein technology platform and IBIO-202’s N-directed approach were validating takeaways from the World Vaccine Congress. ?
Q. In your role as iBio's lead on animal health, you're familiar with infectious disease epidemics among animals and international efforts to contain them. Are there similarities to public health??
Large-scale disease outbreaks are constant challenges within the animal health community, and there are some lessons we can learn in public health. There have been many collaborations among intergovernmental organizations, such as CEPI (Coalition for Economic Preparedness Innovations), academia, and pharma, for rapid R&D and vaccine manufacturing for animal health that could serve as models for public health. How do you identify events? How do you collaborate among organizations with different interests to deliver something meaningful and productive? How can organizations that might not traditionally work together prepare for pandemics in livestock, public health, or for a potential zoonotic event? When you stay so narrowly in your own lane, you don't know what you don't know.?
If we can learn to forge not just domestic partnerships but the international collaborations required to combat pandemics, we'll be better prepared for future outbreaks. There also must be continuity in funding as well as with relationships and networks in times when we're not in emergency-response mode. We have to stay engaged as a global scientific community, or we haven't learned anything.?
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