A new test developed by researchers at The Pirbright Institute, in collaboration with the University of Queensland and the University of Oxford, can detect antibodies that prevent cell-to-cell fusion, a method some viruses use to infect neighbouring cells. The new test is a valuable tool for analysing the antibody response against multiple viruses, including respiratory syncytial virus (RSV), Nipah virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. The method can be used in tandem with other tests to assess the effectiveness of vaccines, therapeutics and antivirals.
Most antibody tests focus on detecting neutralising antibodies, which block viruses from entering the cell to prevent infection. However, some viruses spread by forcing the cells they infect to fuse with their neighbours, creating multi-nucleated cells known as syncytia. Up until now, there were limited tools to assess whether the neutralising antibodies could also prevent these cell fusion events and whether halting this process would result in better protection against the virus.
Studies described in the Journal of General Virology demonstrate that this new method, dubbed the micro-fusion inhibition test (mFIT), can determine whether antibodies are effective at preventing syncytia formation, which can facilitate further research into whether this characteristic improves the protection offered by antibodies.
Cell fusion is used by viruses such as RSV and Nipah virus to spread, and there is growing evidence that SARS-CoV-2 can also cause syncytia formation. In their paper, the researchers demonstrated that the spike protein of SARS-CoV-2 can induce cell to cell fusion; however, the importance of this to natural infections remains to be determined.
To investigate if antibodies against these viruses could prevent syncytia formation, scientists used the mFIT in a variety of applications. This included assessing therapeutic antibodies for RSV and Nipah, evaluating antibodies raised in response to Nipah vaccines in pigs, and examining the ability of SARS-CoV-2 therapeutics to prevent cell fusion. The mFIT was also used to show that antibodies from recovered COVID-19 patients could prevent the formation of syncytia, allowing the team to characterise an important sub-class of SARS-CoV-2 antibodies, which may provide an additional indication of immunity.
Pirbright scientists are now actively using the mFIT to assess a number of COVID-19 vaccines to provide more in-depth information about the immune responses triggered, as part of extensive collaborations within the vaccine development field.
Dr Dalan Bailey, head of the Viral Glycoproteins Group at Pirbright said: “The broad applications of this test, alongside its reliability and high throughput nature, make the mFIT a valuable tool that can be used in tandem with standard neutralisation tests to provide new insights into the importance of cell fusion in infection and immunity. This test gives us additional markers to assess when developing vaccines, antivirals and therapies and could ultimately help us to improve their effectiveness.”
Notes to editors
This research was funded by the Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC), both part of UK Research and Innovation (UKRI). This research was also funded by the Department of Health and Social Care as part of the UK Vaccine Network (UKVN), a UK Aid programme to develop vaccines for diseases with epidemic potential in low and middle-income countries (LMICs).
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
With an annual income of £35 million from grants and commercial activity, and a total of £25.2 million strategic investment from BBSRC UKRI during 2019-2020, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
About the MRC Weatherall Institute of Molecular Medicine at the University of Oxford
The MRC Weatherall Institute of Molecular Medicine (MRC WIMM) was founded in 1989 by Sir David Weatherall, and was the first institute of its kind in the UK to link basic research in molecular and cell biology with clinical research. The MRC WIMM is a strategic partnership between the Medical Research Council and the University of Oxford. The institute brings together over 500 researchers, staff and students now focusing on five research areas: rare genetic diseases, haematology, immunology and infection, stem cell and developmental biology, and cancer biology. www.imm.ox.ac.uk
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The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation (UKRI), a non-departmental public body funded by a grant-in-aid from the UK government.
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