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Three more studies are being funded by the NIHR Oxford Biomedical Research Centre (BRC) to look at the way the body interacts with COVID19; these include assessing the safety of a new vaccine; the role that antibodies might play in plasma therapy; and blood biomarkers that determine adverse reactions in those that have been infected. These three new studies follow three others announced on 6 April.

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Vaccines

One of the new studies, being conducted mainly in the BRC’s Vaccines Theme, is a comprehensive analysis of the various responses to the new COVID-19 vaccine being developed by University of Oxford researchers.

The vaccine trial, which received crucial early funding from the Oxford BRC, has already recruited over 400 healthy volunteers and is expected to begin vaccinations later this week, once final approval is given.

The team – including Prof Sarah Gilbert and Prof Adrian Hill of the University of Oxford’s Jenner Institute and Prof Andrew Pollard of the University’s Oxford Vaccine Group – are testing the new ChAdOx1 nCoV-19 vaccine, which is based on an adenovirus vaccine vector. The trial will provide valuable information on the safety aspects of the vaccine, as well as its ability to generate an immune response against the virus.

The new study, which is led by Prof Pollard and Dr Daniel O’Connor, will use multi-omic techniques – including whole blood transcriptome and plasma proteome — to give a high-resolution description of the immune responses in individuals with COVID-19 disease.

This will allow an in-depth analysis of any COVID-19 cases that occur in nCoV19 vaccinated individuals, and a detailed comparison with unvaccinated controls.

Prof Pollard, the BRC’s Co-theme Lead for Vaccines, said: “We expect these data to give us a comprehensive characterisation of the responses to SARS-CoV2 in nCov19 vaccinated individuals, and help us to get a complete assessment of how safe this novel coronavirus vaccine is.” 

“The data we get in this study will, we hope pave the way for a detailed molecular characterisation of the safety and efficacy of this vaccine, especially for groups at higher risk of severe infection

Immunity

One of the researchers involved in this study is Prof Paul Klenerman, the BRC’s Co-theme Lead for Gastroenterology and Mucosal Immunity. He is leading another of the new studies to receive BRC funding, part of a larger piece of research looking at COVID-19 immunology.

The study is looking at the potential role particular antibodies might play in conferring immune protection to COVID-19, and whether this might be the basis for a possible therapy using plasma for people who have recovered from the virus.

Scientists are currently looking at two different antibody tests, one that tests for any antibody that can bind the virus, and another for antibodies that interfere with infection, so called neutralising antibodies.

The researchers are using this second test to screen potential donors who have recovered from COVID-19 and whose plasma can be donated to people who have contracted the virus. The test will also be used, alongside other tests that are being developed in Oxford, to monitor the effect on the patients and their immune system before and after the plasma is given.

Blood biomarkers

The third study to receive funding is led by researchers from the BRC’s Haematology Theme and includes investigators from the Gastroenterology and Mucosal Immunity Theme.

The study is evaluating the blood cell-related biomarkers that predict adverse outcome in COVID-19 infection.

Researchers will collect samples and clinical data from 100 patients admitted to Oxford University Hospitals ICU and Haematology services to see if they can identify the biomarkers that predict the lung injury and other adverse outcomes, in particular thrombosis, which are associated with COVID-19.

In this study, the research team is testing if acute respiratory distress syndrome (ARDS) and hypoxaemia – an abnormally low concentration of oxygen in the blood – is caused by:

  • myeloid cells being activated in an abnormal way either directly by SARS-CoV-2, or the immune response to the virus;
  • a genetic predisposition in some individuals, called clonal haemopoiesis, theincidence of which increases with age and causes a pro-inflammatory state;
  • a pro-thrombotic state
  • defects in iron haemostasis, which can influence the outcome of infection.

“If we can identify the right biomarkers, it will help to identify those patients who should be prioritised for clinical trials such as the RECOVERY or SETUP trials, to reduce the likelihood of lung damage and thus improve chances of survival,” said Dr Nicola Curry, BRC Co-theme Lead for Haematology, who is jointly leading the study.

“Equally, if we can gain a clearer idea of why certain patients experience these adverse outcomes, we can not only devise new therapeutic interventions, but also develop more effective care pathways for these patients.

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