Vaccines and various response rates


DDW Editor Reece Armstrong speaks to Dr Katrina Pollock from the Oxford Vaccine Group at the University of Oxford. Dr Pollock is the Chief Investigator of the LEGACY03 clinical trial, a study aiming to investigate lymph nodes and vaccination responses across age groups.

RA: Could you tell us about the LEGACY03 trial? 

KP: The LEGACY03 study aims to understand how we respond to vaccines and how this changes as we age. The study will recruit 48 participants over two winter seasons in 2023-2024 and 2024-2025. Participants have a Covid-19 and seasonal flu vaccine, and donate blood and lymph node cells to monitor the response. 

RA: Why do vaccine responses vary across patient populations, in particular elderly people? 

KP: Our immune system changes across different life stages. As we age, in adult life, changes in immunity, in particular in immune cells, affect how we respond to vaccines. This change in our ability to respond to vaccines also makes us vulnerable to infectious disease. 

RA: Why have you selected lymph nodes as the target for vaccine responses in this study?

KP: Lymph nodes are small bean-shaped organs and there are hundreds throughout the body. When we have a vaccine as an injection in the arm, lymph nodes in the armpit respond to the vaccine. It is these lymph nodes which help to make proteins called antibodies that protect from infection. 

RA: What end results do you hope to gather from this study?

KP: Our research is investigating these lymph nodes in detail to see whether they differ in younger and older people. Cells from responding lymph nodes are collected by means of ultrasound guided fine needle aspiration after immunisation in the arm. This is an established test in the clinic. In research, it allows us to directly study vaccine-responsive cells, for example their genomic composition and protein expression. We can compare these readouts in different groups of people. 

RA: How can results of this study benefit vaccine design in the future? 

KP: Our goal is to use these data for the transformative understanding of the human immune system and how it interacts with vaccines. By directly studying the cells that actually respond, we can build a detailed picture that will enable the discovery of new vaccines. In this way, we will have early readouts of potency that we can apply to new vaccines as they become available to feed back into vaccine design.

RA: Could you discuss the collaborative nature of this project? 

KP: Our research is conducted by a multidisciplinary team of clinicians, scientists, and research nurses, and is a collaboration of different research sites with specialist facilities. The Experimental Medicine Clinical Research Facility is a collaboration between the University of Oxford and the Oxford University Hospitals NHS Foundation Trust. It houses the lymph node imaging and biopsy capabilities for the study led by Cushla Cooper. The Oxford Vaccine Group manage the overall study and immunisations in their specially-designed research facility. 

RA: How much do we currently know about vaccine response rates, in particular for flu and mRNA-based Covid vaccines? 

KP: Large scale phase IV and post licensure studies of Covid-19 mRNA vaccines and seasonal flu vaccines have found them to be effective in controlling disease. Responses to vaccines are not equal across different subtypes of flu, different variants of SARS-CoV-2 and in different patient groups however. It is these differences in immune response, which have stimulated our research to improve vaccine design. 

RA: Any future plans to assess response rates in other types of vaccines? 

KP: Our team are interested in assessing how lymph nodes in people of different ages respond to vaccines against infections that they have never encountered before. We are designing research to test vaccines against pathogens that could cause the next pandemic.  

DDW Volume 25 – Issue 2, Spring 2024

Dr Katrina PollockBiography:

Dr Katrina Pollock is an MRC Clinician Scientist in Vaccinology at the Oxford Vaccine Group, University of Oxford. She read medicine at the University of Cambridge and Imperial College London before training as a clinician scientist. She leads an experimental medicine programme to investigate human lymph nodes responses to immunisation.


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