While future viral outbreaks are inevitable, the Flagship Origination Partner and Apriori Bio Co-Founder and CEO explains we now have the tools to beat them.
Headlines warn of yet another variant of SARS-CoV-2 as we play what Ed Yong aptly called in The Atlantic “a continual cat-and-mouse game” with the virus. While vaccines have dramatically reduced hospitalizations and saved countless lives, new variants are emerging and slipping past our immune defenses, leaving us steps behind in our efforts to curb the pandemic. Ultradynamic viruses like SARS-CoV-2, Influenza, and HIV mutate rapidly, making it challenging to develop and deploy vaccines that provide durable protection from infection. Scientists at Flagship Pioneering turned their attention to such viral threats to envision a future in which we could predict potential variants of concern and develop vaccines against them before an outbreak. This exploration led to the founding of Apriori Bio and the company’s Octavia™ platform that is enabling new vaccines and antibody drugs that protect against current and future viral threats. To understand more about this new company and its timely efforts, we spoke to Apriori Bio CEO and Co-founder and Flagship Origination Partner Lovisa Afzelius.
How is Apriori changing how we approach vaccination?
Vaccines trick the immune system into producing an antibody response by using a protein present in a virus. If the immune system then encounters that protein, it is already equipped to respond, preventing disease or reducing the severity of disease. Mutations in the viral RNA give rise to variations in those target proteins that the immune system may not be able to recognize as the same threat. Apriori has the tools to predict future variants of concern and understand the totality of the current and future variant space. Our engine Octavia allows us to rethink the entire paradigm of vaccination, defining the antibody repertoire needed for protection now and in the future. With this insight, we can design antigens to elicit the necessary immune response for continual protection, creating what we call variant-proof vaccines.
Our engine Octavia allows us to rethink the entire paradigm of vaccination, defining the antibody repertoire needed for protection now and in the future.
How did the COVID-19 pandemic impact your development of Octavia?
The COVID-19 pandemic increased the urgency of our work, while also increasing our ability to move fast because we could constantly pressure test our platform as the pandemic evolved. One of the biggest moments for us was when we modelled SARS-CoV-2 data that revealed the staggering impact of mutations: In June 2020, the U.S. had approximately 150,000 deaths, which was with the infectivity rate, the viral transmission rate, and case fatality rate of the original Wuhan strain. If this original strain had the same infectivity rate as the current variant, BA.5, which is similar to measles, but the same case fatality rate as Wuhan, we would have had approximately 3.5 million deaths in that same time period. This understanding enhanced our conviction that we must gain control over viral threats and not continue to leave ourselves vulnerable.
Other researchers are using AI and ML to predict variants of concern, how is Apriori taking this a leap forward?
We call Octavia a biology-informed artificial intelligence engine, meaning we are using massive experimental datasets sets to train our algorithms, which allows us to constantly evolve our models to include larger and larger variant spaces. We're building a platform that could be modified for any viral threat that could emerge. What also sets the Octavia algorithm apart is its ability to assess the impact of multiple mutations at the same time, which is a hard problem to model that it handles as well as it predicts single mutations. Through the combination of high-throughput biological systems and AI, we are able to artificially describe spaces that would be impossible to describe experimentally. For example, if you look at the receptor binding domain of SARS-CoV-2, which is about 200 amino acids, introducing seven mutations or substitutions would give 1021 theoretical combinations. This number is so large that if every person on earth dedicated themselves to working on this one problem, it would take as long as the universe has existed to test all of these variants.
We're building a platform that could be modified for any viral threat that could emerge.
How do you envision Octavia supporting public health policy?
We should be prepared for future pandemics, and public health officials need to be able to distinguish between levels of risk as part of that preparedness, enabling more explicit and targeted public health guidance. An ability to track and assess viral threats as they emerge, much like our hurricane alert systems does for storms, would allow governments to provide this type of information to the public. Octavia would be an essential part of such an alert system that could instantly assess the risk of a particular sequence — imagine knowing instantly whether a sequence could escape current vaccines. While our core focus is on developing improved vaccines and antibodies, we believe that we have a responsibility to provide and share insights with governments across the world for the benefit of all.
Why is a tool like Octavia so critical now and in the future?
It is inevitable that we will face additional pandemics. It is not a question of if but when, and Octavia is enabling us to get ahead of these threats by predicting mutations of concern and plotting out their potential escape routes. This is critical now as we struggle to effectively respond to SARS-CoV-2, Influenza, and HIV, but it is also important for the future in addressing other ultradynamic viruses that may emerge. By engineering variant-proof vaccines and antibody drugs, Apriori is working to maintain and improve our collective health security.
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