This study will test the responses of cells in lymph nodes before and after immunization with flu and COVID-19 vaccines and compare reactions in older and younger adults.

• The new study will measure how lymph nodes respond to vaccines and how this reaction changes as we age
• Results will contribute to future vaccine design which will offer greater protection to those most vulnerable to diseases such as flu and COVID-19 and also those better suited for younger people
• Project to be led by Principal Investigator Dr Katrina Pollock, MRC Clinician Scientist in Vaccinology at the Oxford Vaccine Group, based at the Department of Paediatrics, at the University of Oxford
• £1.95 million funding from the Medical Research Council/UK Research and Innovation, sponsored by the University of Oxford

A pioneering study into human immunity is being launched today by Oxford Vaccine Group at the University of Oxford. The study, called LEGACY03, is being funded by the Medical Research Council part of UK Research and Innovation. By investigating how lymph nodes work, and how they make responses to vaccines in younger and older people, it has the potential to improve vaccine design for different age groups significantly.

The study is looking to enrol volunteers aged either between 18 to 45 years OR 65 years and over at the time of screening, and will be based at the Centre for Clinical Vaccinology and Tropical Medicine, based at the Churchill Hospital in Oxford. Participants will enrol for 3 months and the results will assist researchers to design vaccines that offer greater protection to those most vulnerable to diseases like flu and COVID-19, particularly older people. It will also enable scientists to design vaccines better suited for different age groups throughout life.

As we age, our immune system changes and with it our response to vaccines. Our risk of complications from infections like flu and COVID-19 also increases and it is therefore important to understand these changes so that vaccinations can be better tailored for maximum efficacy to protect the most vulnerable.

As part of my work as a clinician scientist I was keen to improve understanding of the immune system in people and to respond to the challenges in adult vaccinology which are predominantly two-fold: The first major challenge is the diversity of responses to vaccines in different people, particularly the most vulnerable like older adults or those living with conditions that affect immune function. The second major challenge is making vaccines for targets that rapidly evolve, like COVID-19 and HIV. This study will take an innovative look at individual immune responses using vaccinations as a tool to investigate human immunity at the cellular level. This will help us to tailor future vaccine design to get a better outcome for patients across the board. It has the potential to impact patients for the better and that is what drives my research."

Dr Katrina Pollock MRC Clinician Scientist in Vaccinology at the Oxford Vaccine Group, Department of Paediatrics

Lymph nodes are small bean shaped organs present all over the body. After a vaccine is given in the arm, white blood cells go to the site of the injection and they take some of the vaccine back to the lymph nodes in the armpit. This is where the response happens.

Instead of just measuring the output of the vaccine, which is the antibodies in the blood, the LEGACY03 study will visualize the lymph nodes themselves using an ultrasound scanner and at the same time take a small number of cells from those lymph nodes to see how they are responding. Paired with information about what is happening in the blood, scientists can establish a detailed picture of how different vaccines work.

Participants in the study will receive two vaccines: an mRNA COVID-19 booster vaccine and a seasonal flu jab. Both have been licensed for use in adults and the seasonal flu vaccine is recommended for older adults.

Cells from the lymph nodes will be sampled using a technique called fine needle aspiration (FNA) which is a safe and well-tolerated procedure that involves taking cells and fluid from a lymph node using a fine needle. A video showing the technique and detail on the study is available to watch here https://www.youtube.com/watch?v=GXkikTKWfnY