Tapping Into Information Locked in Our T Cells To Fight COVID-19

Our immune system is instrumental in protecting us from external invaders of every shape and size. If it isn’t part of us, our immune system will fight it, or at least try to.

The innate immune system is our first line of defense and combats all intruders without discrimination. Our bodies longer term plan, however, involves the adaptive immune system – the strategic troops that identify and respond to specific foes and add them to the body’s “little black book” to remember for next time – the immune memory.

Most of us are probably familiar with the part that antibodies play in this scenario, especially with the coverage in relation to the ongoing COVID-19 pandemic. However, T cells also have a vital role in this process. They are a mine of information with regards to the way our bodies perceive and respond to pathogens, information that can be valuable for guiding the development and refinement of effective therapeutics and preventatives.

We spoke to Dr Harlan Robins, Chief Scientific Officer and Co-Founder of Adaptive Biotechnologies, about what we can learn from T cells in relation to  disease and immunity, how they are harnessing that information and how researchers are using it in the fight against COVID-19.

Karen Steward (KS): The adaptive immune system is incredibly complex and shows great variability between individuals. How do you “measure” the adaptive immune system, what tools and techniques are key to this process?

Harlan Robins (HR): The adaptive immune system detects and treats most diseases in exactly the same way. The immune system works through specialized cells of the adaptive immune system – T cells and B cells each have receptors on their cell surfaces that act as scanners, constantly looking for diseases. Our immune cells have evolved to be massively diverse to protect us from millions of different signals of disease that our bodies encounter every day. Every single person presents disease a little bit differently in their own immune system, and we have evolved this way as humans to ensure that no virus or germ can completely eradicate the human race.

Over the ten past years, Adaptive built an immune medicine platform to read and translate the genetics of the adaptive immune system into clinical diagnostics and therapeutics based on how the immune system naturally detects and treats disease. This is a very hard but solvable big data problem if you have the right technology and the right minds behind it.

In 2018, Adaptive forged a partnership with Microsoft to bring together their AI, machine learning, and cloud computing to our immune medicine platform which is based on high-throughput next-generation sequencing of these immune receptors. This partnership accelerated our ability to map the trillions of T-cell receptors (TCRs) to the millions of clinically relevant disease antigens to which they bind. Together we aim to translate the natural diagnostic capability of the immune system to the clinical setting to build the TCR-Antigen Map. This will make it possible to read what an immune system has fought or is currently fighting, with the goal of creating a better diagnostic for all diseases—from cancer to autoimmune conditions to infectious diseases.

When the pandemic struck, we were able to turn the machinery we already had in place quickly toward decoding the immune response to COVID-19. Through our platform, we can identify the T cells activated in response to the virus – at both an individual level and population level – and measure their response over time to answer important questions about the virus itself and immunity.

KS: Most people are familiar with the role that antibodies play in establishing long-term immunity. Can you tell us about where T cells fit into the long-term immunity picture and their potential role in vaccination?

HR: As more SARS-CoV-2 vaccine data and other research becomes available, we’re learning that antibodies don’t seem to tell the whole story about immunity.

T cells are the adaptive immune system’s first responders to any virus, and they are a measure of past infection and, ultimately, immunity. However, until recently, the technology hasn’t existed to study T cells at scale – that’s why so much of the conversation has centered around antibodies.

When a virus appears, the T cells quickly multiply to attack the virus and recruit B cells to produce antibodies that potentially provide protection against future infection. An important characteristic about T cells is that they can “remember” past infections and kill pathogens if they reappear. This is significant because antibody signals for SARS-CoV-2 have been reported by many researchers to decline over time. Additionally, recent research has shown that the T-cell response can persist even when antibodies wane. Our own analysis from our ImmuneCODE™ database shows that T-cell responses persist as long as 90 days, the current limit of our samples, making it a reliable measure of past and current infection that can potentially help define immunity, which will be critical in vaccine trials.

KS: Please explain for readers who may be unfamiliar with them what the ImmuneCODE database is and how that data led to the newly launched immunoSEQ T-MAP COVID? How do they differ to conventional immune system measures?

HR: Leveraging our immune medicine platform with Microsoft’s machine learning capabilities, we launched ImmuneCODE™ in June, which represents the largest database of T-cell immune response to SARS-CoV-2 across the population. All the T-cell response data that we’ve collected so far is being made freely available to the scientific and public health communities to help accelerate solutions.

Measuring the T-cell response, as opposed to the antibody response, represents a significant shift in the way we, as a society, have been evaluating the immune system and viruses. Currently, existing tests either evaluate the presence of a virus for current infection (PCR testing) or measure the antibody response for evidence of previous infection (serology testing); however, researchers from around the world have been publishing studies showing that antibodies don’t tell the whole story about the immune response to the virus.

Using T-cell data from ImmuneCODE, we were able to do two things. First, we launched immunoSEQ® T-MAP™ COVID -- a new tool for vaccine developers to integrate into their trials to accurately and reproducibly measure the T-cell immune response to vaccines and track the persistence of that response over time using a small blood sample. Secondly, Adaptive is also completing validation of a clinical T-cell based diagnostic to broadly identify past exposure reliably and reproducibly. We are pursuing an Emergency Use Authorization (EUA) from the FDA for use of this diagnostic test called immunoSEQ Dx® SARS-CoV-2.

KS: How is information in immunoSEQ T-MAP COVID assisting COVID-19 research? Is the data available to all researchers?

HR: Adaptive and Microsoft are making the data from ImmuneCODE™ freely available to researchers, government, universities and anyone looking to advance solutions to the pandemic.

We are generating an unprecedented amount of T-cell data – using samples from over 4,500 patients from around the globe. To date, we have analyzed more than 1,400 samples, including samples from our virtual, prospective study ImmuneRACE.

Specifically, the clinical utility of this data can help to map virus-specific TCR responses, antigens and viral genomes, and inform design of vaccine targets. With continued expansion and additions to the database, it could ultimately inform therapeutics, vaccines, treatments and help to define immunity to SARS-CoV-2.

Our data is publicly available to all researchers here.

KS: Can you tell us more about the T-cell-based diagnostic for SAR-CoV-2 that Adaptive are also developing?

HR: T cells hold a treasure trove of information that is important for tracking a measurable immune response to COVID-19.

Based on data from ImmuneCODE™, we are creating a T-cell based diagnostic test to detect past infection in a real-world setting. Based on our current research, we are seeing that the T-cell test performs favorably against two leading serology tests, the results of which we plan to publish soon. We are in active discussions with the FDA and are confident we will launch a test in the fall with a comparable label to serology tests.

In addition, we plan to expand the use of this test to include: (1) post-infection immunity, and (2) immunity from a vaccine. We are also working to develop a separate test to assess pre-existing immunity based on cross-reactive T cells.

KS: How do you foresee this level of information on adaptive immune responses impacting monitoring, testing and treatment in a healthcare setting in the future?

HR: We believe that by making our data freely available to the global research community, we are improving our collective understanding of how our bodies naturally detect and respond to COVID-19, which can provide population-level insights on disease patterns. This data is intended to empower the scientific community to accelerate the development of new diagnostics, vaccines and therapeutics.

We hope that this type of collaboration and data sharing prompted by the pandemic will continue and will help us get head of future pandemics.

Dr Harlan Robins was speaking to Dr Karen Steward, Science Writer for Technology Networks.