Understanding Chronic Inflammation Through Viral Exposure

In this Pharmaceutical Executive video interview, Nigel McCracken, chief operating officer, Virax Biolabs, discusses results from new data on the role of T cell dysfunction in post-acute infection syndromes (PAIS) at the World Immune Regulatory Conference in Switzerland. These syndromes are characterized by persistent, often debilitating symptoms that linger long after the initial infection has resolved. With growing recognition of the immune system’s role in driving these conditions, Virax's research focused on identifying biomarkers of immune exhaustion to better understand and potentially diagnose PAIS.

Pharmaceutical Executive: How does the ViraxImmune PAIS assay differentiate between healthy individuals and those with PAIS based on cytokine levels?

Nigel McCracken: The ViraxImmune post-acute assay we’re developing measures the specific T cell response when stimulated with an array of infection-derived peptides. In cases like COVID-19, most people think only of SARS-CoV-2, but it's possible that SARS is just one of several viruses pushing the adaptive immune system beyond its limit. Over the course of our lives, we're exposed to many viruses.

Take herpes virus, for example—when someone is run down, they might develop a cold sore. That’s due to a weakened immune system. Our test evaluates general immune function by analyzing specific cytokines, but it also assesses responses to individual viruses using tailored peptide mixes. This dual approach allows us to detect immune dysfunction while also pinpointing its cause—whether it's a single virus or a combination of viral exposures that the immune system hasn’t fully cleared.

During the pandemic, we often heard about patients being hospitalized due to cytokine storms—an overactive immune response that can lead to organ failure. In cases of immune dysfunction, the immune system may realize it can’t clear the virus without harming the body, so it maintains a prolonged response. The problem is that T cells remain continuously activated, leading to chronic inflammation. While inflammation is useful in fighting infections, it can be harmful if sustained over time.

Full Interview Summary: At the recent World Immune Regulatory Conference in Switzerland, Virax Biolabs presented pivotal findings on T cell dysfunction in post-acute infection syndromes (PAIS), such as long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and chronic Lyme disease. The team explored how persistent immune activation post-infection leads to T cell exhaustion, a phenomenon well-documented in oncology but now increasingly relevant in chronic infectious conditions. Their study demonstrated that prolonged antigen stimulation in vitro caused upregulation of key exhaustion markers—PD-1, LAG-3, TIM-3, TIGIT, and CD39—on both CD4+ and CD8+ T cells. These markers were associated with impaired cytokine production, helping to distinguish individuals with PAIS from healthy controls.

Virax’s post-acute assay, under development, measures T cell cytokine responses after stimulation with peptides derived from various viruses, including SARS-CoV-2 and latent viruses like herpes. This dual-layered approach allows for detection of general immune dysfunction and identification of specific viral triggers. Importantly, it highlights how chronic antigen exposure can leave the immune system in a prolonged inflammatory state, unable to fully clear infections or return to baseline.

Beyond PAIS, Virax aims to extend its immune diagnostic platform into broader areas such as transplant medicine and oncology. In transplant patients, monitoring latent viral reactivation and immune competence could prevent complications like organ rejection. In oncology, particularly with CAR-T therapies, understanding immune status could inform dosing strategies and predict efficacy and safety. The company is pursuing collaborations with academic research centers in the UK and US, while engaging with the FDA on clinical study pathways. Virax Biolabs seeks to shorten diagnostic timelines, enable earlier interventions, and expand the scientific understanding of immune dysfunction across multiple disease states.