Adenovirus vaccine vectors, such as the ChAdOx1 nCov-19 construct which has risen to prominence as a major vaccine for COVID-19, may generate robust long-term immune system responses, according to scientists from the Universities of Oxford and the Cantonal Hospital St.Gallen, Switzerland.
Writing in the journal Nature Immunology, they detail an investigation into one of the key features of adenovirus vaccines - their ability to generate strong and sustained populations of the 'killer' T-cell element of the immune system.
In an animal model, they observed that adenoviruses are able to get into long-lived tissue cells, known as fibroblastic reticular cells, which in turned formed small, well organised clusters, acting as 'training grounds' for these T-cells, appearing to explain how these vaccines sustain robust immune system responses.
Paul Klenerman, Sidney Truelove Professor of Gastroenterology at the University of Oxford's Nuffield Department of Medicine, and one of the lead authors of the paper, said:
'Millions of people will have received adenovirus vaccines around the world, not only the Oxford-AstraZeneca vaccine, but the J&J vaccine, and also the Chinese and Russian versions. The ultimate goal with these vaccines is the induction of long-term immune system protection using both antibodies and T-cells. This research helps us to understand more on the process of vaccination, and why the effects on killer T-cells are so prolonged.'
The researchers show that adenovirus vectors can target specific cells - known as stromal cells in tissues such as the lung - generating antigen 'depots' in these long-lived cells. These stromal cells were originally thought just to provide an inert scaffold for the tissues, but it appears that they are very dynamic cells with a major role in immune control. The long lived nature of the cells means that the antigen can be 'shown' to the immune system many times, effectively boosting the response, a critical element of generation of protective T-cells.
They were also able to investigate other mechanisms which may explain the particular efficacy of adenovirus vectors, including the key chemical messenger involved in signalling to T cells. This is a factor called IL-33 - a so-called "alarmin" released when the stromal cells receive signals of distress. IL-33 acts to strongly boost to the metabolism of the T cells, resulting in effectively more energetic cells and a highly protective immune response.
Burkhard Ludewig, Professor at the University of Zurich, and Head of the Medical Research Center, Cantonal Hospital St. Gallen, Switzerland, also a lead author of the paper, said:
'Adenoviruses have co-evolved with humans over a very long time, and learned a lot about the human immune system in the process. Viruses are always the best teachers, and here they have taught us an important lesson about how best to boost killer T cell responses. The T cells that come from these cellular training camps appear to have a very high level of "fitness". Hopefully we can put this to good use in designing new vaccines - vaccines that we still desperately need for diseases such as TB, HIV, hepatitis C and cancers.'
The researchers will now continue to investigate these particular pathways for immunization against emerging pathogens, both in pre-clinical models, and clinical studies, with the goal of helping to accelerate further development of crucial vaccines.
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Notes to Editors:
For a copy of the paper, or to request an interview, please contact: burkhard.ludewig@kssg.ch or paul.klenerman@medawar.ox.ac.uk
About the Nuffield Department of Medicine:
The Nuffield Department of Medicine is a large research and teaching department with a grant portfolio of over £700m, 1,000 employees in the UK and 2,000 associated staff overseas programmes. Its aim is to translate scientific discovery into clinical impact and it is known for:
- Integrating basic science and clinical specialities
- Pioneering the use of molecular, structural biology and genetics to study human disease
- World famous major tropical medicine units in Kenya, Thailand and Vietnam, with permanent units in six other countries.
- Drug Discovery programmes, clinical biomanufacturing and clinical trials
- Big Data
- Vaccine Development
- Human Immunology and the study of pathogens
About the Medical Sciences Division
The Medical Sciences Division is an internationally recognised centre of excellence for biomedical and clinical research and teaching and is the largest of the four academic divisions within the University. The other three divisions are Humanities, Mathematical, Physical and Life Sciences and Social Sciences.
Over 5000 academics, researchers, NHS clinicians and GPs, and administrative staff, 1500 graduate and 1600 undergraduate students, together contribute to its extensive and exemplary research, teaching and clinical portfolios.
It aims to be the best university biomedical institution in Europe and amongst the best five biomedical institutions in the world, and has been ranked number one for the last ten years in the Times Higher Education World University Rankings for clinical, pre-clinical and health sciences - the only non-North American institution to be top-ranked by THE in any subject discipline.
About the University of Oxford
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the fifth year running, and at the heart of this success is our ground-breaking research and innovation.
Oxford is world-famous for research excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research sparks imaginative and inventive insights and solutions.
Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 200 new companies since 1988. Over a third of these companies have been created in the past three years.
About the Cantonal Hospital St. Gallen, Switzerland
The Cantonal Hospital St.Gallen is the central hospital in Eastern Switzerland. As one of the largest hospitals in Switzerland, the Cantonal Hospital St.Gallen takes on basic care tasks for the population of the city of St.Gallen as well as central functions for the residents of the entire canton of St.Gallen and the neighboring regions.
The Cantonal Hospital St.Gallen is the academic teaching hospital of the University of St.Gallen. In addition, the Cantonal Hospital St.Gallen is an active research hospital with researchers pursuing projects in basic and clinical sciences. The high quality of the research performed at the Cantonal Hospital St.Gallen is acknowledged by national and international funding agencies such as the Swiss National Science Foundation, the Human Frontiers Science Program and the European Research Council.
Journal
Nature Immunology