Oxford launches LEGACY03 trial to unravel age-related vaccine mysteries

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Vaccines are the most effective way to prevent infectious diseases (NHS, 2023) however, people respond to them in different ways. The elderly and those over 65 particularly tend to respond less well as the immune system matures.

To address the risks this individual response poses to global health, we need to understand how age affects vaccine efficacy. At the University of Oxford, we have a unique culture of collaboration and specialist expertise which means we are well-positioned to investigate these issues. With funding from MRC/UKRI we brought together scientists, radiologists and clinicians to research and understand the cause and effect of varying responses to vaccination.

As part of the recently launched LEGACY03 trial, we're testing the responses of cells in lymph nodes - small bean-shaped organs found all over the body that respond to infection - before and after immunization with flu and COVID-19 vaccines. The aim is to compare the response to these vaccines in older and younger adults.

The study focuses on volunteers aged between 18 and 45 years or 65 years or over at the time of screening. Oxford University's Experimental Medicine Clinical Research Facility (EMCRF) welcomed its first volunteers to the study in November. Their role is to harvest a small number of cells from the lymph nodes and to visualize the lymph nodes themselves using an ultrasound scanner. Paired with information about what is happening in the blood, this evidence enables scientists to establish a detailed picture of how different vaccines work on different people.

We are very excited to receive the first volunteers as part of the LEGACY03 trial. EMCRF is working alongside radiologists from Oxford University Hospitals and the study team from the Oxford Vaccine Group, to conduct these trials and deliver results. This is another great example of collaboration between Oxford University and the NHS Trust aimed at bringing new solutions to enhance patient outcomes and we're pleased to be a part of it."

Cushla Cooper, Clinical Operations Lead for the EMCRF

Dr Katrina Pollock MRC Clinician Scientist in Vaccinology at the Oxford Vaccine Group, and Principal Investigator in the LEGACY03 study said: "We have had over 700 people volunteer to be part of the study which is a phenomenal response to our appeal. The collaborative efforts of academia, clinicians and public volunteers, in tandem with MRC and UKRI funding to support this vital study, mean we can generate meaningful results that will benefit public health globally."

Dr Rajat Chowdhury, senior specialist Consultant Radiologist at Oxford University Hospitals NHS Foundation Trust and Honorary Senior Clinical Lecturer at Oxford University said: "It is a great privilege to be working with our fantastic volunteers and within a dynamic and highly-skilled multidisciplinary team of leading experts in Oxford to develop pioneering disease-preventing medicines that will help protect people all around the world."

Participants in the study receive two vaccines: an mRNA COVID-19 booster vaccine and a seasonal flu jab. The trial is being run by the Oxford Vaccine Group at the Centre for Clinical Vaccinology and Tropical Medicine, and participants are enrolled for 3 months. The results will assist researchers in designing vaccines which will offer greater protection to those most vulnerable to diseases such as flu and COVID-19.

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