New Data Links Chronic Antigen Exposure to Immune Dysfunction in Post-Acute Syndromes

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: Can you elaborate on the key findings from your study on T-Cell dysfunction in post-acute infection syndromes (PAIS) presented at WIRM?

Nigel McCracken: We recently presented data in Switzerland exploring the utility of evaluating T cell dysfunction—or more broadly, immune dysfunction—in post-acute infection syndromes. When we talk about these syndromes, we're referring to conditions like long COVID or chronic fatigue syndrome. These are typically complex conditions that arise when an infection isn’t fully cleared by the immune system.

They’re characterized by a wide range of persistent symptoms—such as chronic fatigue, cognitive issues, and dysfunction affecting various organs—that can last for weeks, months, or even years. In the case of chronic fatigue, many patients have been dealing with symptoms long-term.

From a scientific standpoint, when we look at literature on immune system dysfunction, especially in the context of viral infections, the findings are consistent. Chronic antigen exposure—when the immune system is repeatedly stimulated by viral particles—can impair T cell function. At the conference, we shared data showing this effect by stimulating T cells over a four-day period. After stimulation, we observed upregulation of exhaustion markers such as PD-1, indicating T cell dysfunction.

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.