The current academic year at Oxford began last October with the news that the Nobel Prizes in both Chemistry and Physiology or Medicine had been awarded in recognition of work conducted in the University. Graduate students had made fundamental contributions to that work, one of the Prize Winners in Chemistry was being honoured for work as a student here; and students were leading authors on the papers cited for the Prize in Physiology or Medicine.
Oxford’s response to the SARS-CoV2 pandemic has demonstrated again the power of its research and discovery pipelines, in vaccinology, in structural biology and drug discovery, for clinical trials, in population health, and in data science. We are very proud of the contributions made by our current students based in Oxford and overseas to the University’s efforts against the pandemic, and wanted to share some of them with you as you prepare to take up your place here in the next Academic Year. You will be joining one of the most remarkable research communities in the world, a global community which reflects Oxford’s global reach.
Some of our students were already working in areas close to vaccine development or virology, but others have adapted their projects and/or work to focus on tackling the global pandemic. These students have been based in Oxford and in the University’s overseas units in Kenya, Thailand and Vietnam, as well as at the US National Institutes of Health (NIH).
Students working with Professor Sarah Gilbert and Professor Teresa Lambe within the Nuffield Department of Medicine's Jenner Institute have played a key role in generating a new adenoviral-vectored vaccine as reported widely around the world.
As a DPhil student at the Jenner Institute, I have been part of the lab team working on the clinical trial of the University’s COVID-19 vaccine. This has involved measuring the immune response, particularly the level of SARS-CoV-2 antibodies, in blood samples taken from volunteers. This allows us to determine whether potential recruits have been naturally exposed to this virus prior to their enrolment in the trial. Once volunteers are enrolled and vaccinated, blood samples taken thereafter allow us to measure the immune response elicited by the vaccine. The data we are generating in the lab will provide important context with regards to the vaccine’s eventual efficacy and will further our understanding of the type of immune response required for protection against COVID-19.
As an NIH-Oxford Scholar, Jyothi is mentored by Professors Sarah Gilbert and Teresa Lambe at The Jenner Institute, and Dr. Vincent Munster of the National Institute of Allergy and Infectious Diseases. She is currently based at the NIH Rocky Mountain Laboratories where she has contributed to preclinical efficacy evaluation of The Jenner Institute's COVID-19 vaccine candidate, ChAdOx1 nCoV-19. Currently, she is carrying out further immune profiling of the vaccine response and is beginning immunophenotyping studies in other models of SARS-CoV-2 infection. See Jyothi's recent paper on this research.
Liliana Cifuentes, who is based in the Kennedy Institute, has joined the COVID-19 Vaccinology group on secondment from her main DPhil project. Like others, she is therefore contributing directly to the Oxford leading vaccine candidate against SARS CoV-2 and the ongoing clinical trials of it.
As an undergraduate student within the Emerging Pathogens group at the Jenner Institute, I was involved in the preclinical ChAdOx1 nCoV-19 vaccine immunogenicity studies preceding human trials. These studies served the foundation for current vaccine trials work. Together with fellow DPhil students and postdocs, we have completed a review article detailing the early global landscape of COVID-19 vaccine development efforts. I’m grateful to be surrounded by a team of such incredible, hard-working scientists.
Structure, Drug Screens and Tools
In the Dunn School of Pathology the Ervin Fodor lab has been screening compounds with potential CoV-2 RNA polymerase inhibitory activity using an essay set up by DPhil student Alex Walker. A pre-print from this work is available online. Alex is now supporting several companies to adopt this method for high-throughput screening for polymerase inhibitors.
I am contributing to the characterisation of human antibody and viral spike protein interactions via electron cryomicroscopy. This information provides an insight into how the human immune system combats the infection, thus enabling the identification of weak spots on the surface of the virus that could be used for developing new treatments against COVID-19.
In addition, Dunn School DPhil student Michael Knight is providing essential support for SARS CoV-2 work across the University by being one of the key workers in the Dunn School CL3 lab, using live virus cell culture systems. He is also personally currently working on antibody-mediated neutralization and viral RNA structure.
Profiling host immune responses
Through the Sepsis Immunomics study that I set up, we have recruited a cohort of severely ill COVID-19 patients. We will deploy multiple -omic platforms to comprehensively profile the immune response to SARS-CoV-2 infection and to dissect the disease heterogeneity in COVID-19. To understand the biological context of the immune response, we will compare the immune landscapes across a number of different conditions, including in patients who have suffered from severe influenza infection or bacterial sepsis to understand what is unique about the immune response to COVID-19.
Felix Richter is studying why older adults display such a significant level of mortality with SARS CoV2 infection compared to younger people. Early studies suggest that an exacerbated immune response (cytokine storm) contributes to the increase of disease severity observed in the older patients, and older adults are prone to increased inflammation (“inflamm-aging”). Felix is exploring whether an age-related decline in autophagy within immune cells is a key contributor to inflamm-aging, and searching for novel drugs that may counteract it. Felix, a Nuffield Department of Medicine students is based in the Kennedy Institute for Rheumatology, part of the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS).
In the Nuffield Department of Primary Health Care Sciences, DPhil student Nick DeVito has set up a website tracking the SARS CoV-2 research landscape, covid19.trialstracker.net and with students Liz Morris, Kome Gbinigie, Clare Goyder, Lucy Abel and Jienchi Dorward contributed multiple articles to the University’s Centre for Evidence Based Medicine online presence: CEBM COVID-19 Evidence Service covering proposed treatments, diabetic risk, and mortality data.
Jennifer Lane and Albert Prats-Uribe
NDORMS students Jennifer Lane and Albert Prats-Uribe are part of the core team of a large observational data science network involving 300 researchers from 30 nations working on a combined effort to better understand SARS CoV-2. Jennifer is the lead author as part of a team studying the role of hydroxychloroquine treatment in combination with azithromycin. This paper is still under review but has received significant media attention from Forbes, Science magazine and MedPage and led to changes in regulatory guidance by the European Medicines Agency, and her hydroxychloroquine work in the context of the SARS CoV-2 pandemic is continuing to develop.
DPhil student Claire Lunde (Nuffield Department of Women's and Reproductive Health) is working with The Endo Care Team and Endometriosis UK who have launched an impact survey for women living with Endometriosis during the COVID-19 pandemic. It aims to identify how the pandemic has impacted access to healthcare, diagnosis, and if it has elevated levels of anxiety and depression.
DPhil student Jossey Agyeman-Duah (also NDWRH) is providing honorary service to a philanthropic organisation in drafting the technical content of their COVID-19 preparedness and emergency support to select African countries. Her work has included conducting needs assessment through interviews and engagement with local country experts, background readings and analysis, and report writing. Jossey says: "I'm proud to have had the chance to contribute to efforts in fighting this pandemic."
Neutralising Antibodies and Protein Vaccines
Meanwhile, in the Weatherall Institute of Molecular Medicine the Townsend lab has been working hard on a second vaccine candidate as well as identifying and characterising several neutralising monoclonal antibodies isolated from Covid-19 patients in the search for a potentially therapeutic antibody. DPhil student Robert Donat has been assisting with antibody characterisation and in particular affinity and kinetic analysis of the antibodies.
Students and alumni from the MSc in International Health and Tropical Medicine, Centre for Tropical Medicine and Global Health, are involved with a broad range of SARS CoV-2 related activities. Many of the current students have shifted their third term projects to contribute to Covid-19 research efforts. Of a cohort of 23 students, 13 are undertaking Covid-19 related research. Projects include: mapping Covid-19 research activity to the WHO research priorities; managing Covid-19 outbreak among migrant workers, refugee populations and informal settlements; examining the unintended consequences of Covid-19 on HIV programmes in Cameroon and Malaria programmes in Nigeria; modelling Covid-19 interventions in Thailand and Bangladesh; Interrogating the ethical implications of Covid-19 interventions in Zimbabwe; exploring the balance between individual rights and social welfare in response to Covid-19; examining the implications of Covid-19 interventions on adolescents in Malawi.
From the MSc in Clinical Embryology, student Kate Stanley initiated research on whether the different cells that make up the male and female reproductive systems are susceptible to infection by SARS-CoV-2, the virus responsible for COVID-19. The results are published in Fertility and Sterility and are generally reassuring for both IVF and natural conception during the current pandemic.