The University of Oxford is to benefit from $2 million (£1.49 million) in funding from the Chan Zuckerberg Initiative (CZI) to investigate how our ancestry and diversity influence the way that vaccines work in our cells.
In partnership with Imperial College London and the Uganda Virus Research Institute, the Lymph nodE single-cell Genomics AnCestrY (LEGACY) Network will create an ethnically diverse single-cell atlas of the response to commonly used vaccines such as flu vaccine with a focus on responses in lymph nodes. The LEGACY vision is to understand and ultimately to predict how humans respond to vaccination at a single-cell level, whilst simultaneously creating universally available on-line materials as resources for further research.
The Oxford team includes a number of investigators across several departments:
- Dr Calliope Dendrou and Dr Anita Milicic (Nuffield Department of Medicine);
- Profs Mark Coles and Brian Marsden (Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences);
- Prof Hashem Koohy (Radcliffe Department of Medicine); and
- Prof Teresa Lambe and Dr Samantha Vanderslott (Paediatrics).
The Oxford researchers will analyse samples provided by Imperial College using single-cell technology and genetic, functional and serological assays to generate the atlas and data resource. The funds cover the costs of sample analysis, creation of the team performing the functional and computational analyses, community outreach initiatives and training costs for capacity building in Uganda.
Such projects have the potential to significantly advance understandings of how vaccines stimulate immunity across ethnicities and provide new insights for future efforts in vaccine design. This is important, given that the COVID-19 pandemic demonstrated how emerging infections can disproportionately affect different ethnic populations. Combating global infectious threats to human health also requires vaccine development at an unprecedented speed, as exemplified by the ground-breaking COVID-19 research generated by Oxford.
The resources created by the LEGACY Network will serve as a foundation for overcoming differences in vaccine efficacy associated with ancestry, and for accelerating and promoting equity in vaccine research. Fundamental to its vision is community outreach, engaging ethnic minority communities in the UK, and also building capacity in low- to medium-income countries (LMICs) to perform single-cell research in this area. This is critical as LMICs often shoulder a disproportionate burden of major infectious diseases.
CZI Program Manager for Single-Cell Biology Norbert Tavares, said: ‘To create effective treatments and cures for all people, the biomedical community must work to increase representation in scientific research. About 80 percent of current genomic data is from people of European ancestry, which has to change.
‘The Ancestry Networks for the Human Cell Atlas will bring a much-needed perspective to single-cell research and provide key insights into how ancestry impacts healthy and disease states and has the potential to inform the path to treatments.’
Dr Calliope Dendrou, a Sir Henry Dale Fellow and Equality, Diversity and Inclusion Champion from the Wellcome Centre for Human Genetics, and the lead from the University of Oxford, said: ‘Lymph nodes are small organs that are home to the cells that respond to vaccines. Remarkably, very little is known about how they work in humans after vaccination and even less is understood about how ancestral diversity could affect this.
‘Now we have the chance to study them at the single-cell level for the benefit of all. Moreover, we aim to democratise research in this field by providing clinical, experimental and computational training to junior clinicians and scientists from LMICs, and leaving a legacy of empowered and aspirational researchers.’
Dr Anita Milicic, a Principal Investigator at the Jenner Institute, said: ‘This study will perfectly complement ongoing CZI-supported work looking at early responses to vaccine components called adjuvants in isolated lymph nodes from people of different ancestries.
‘Together, these two projects have the potential to significantly advance our understanding of how vaccines stimulate immunity across ethnicities and provide new insights for our future efforts in vaccine design.”
Prof Hashem Koohy, a Co-PI of the project and an Associate Professor of systems immunology in MRC HIU, said: ‘The LEGACY Network project is a very exciting multi institutional and multidisciplinary effort that aims to provide deeper insights into vaccine-induced differential immune response at single cell level in an ethnically diverse population.
‘The existing single cell data that build our prior knowledge of human diseases are mainly biased by European ancestry. The LEGACY Network provides an opportunity to study differential immune response to vaccines in the light of diversity and ancestry.’
Further $2m CZI boost for NDORMS musculoskeletal atlas research
An additional $2 million from the initiative was granted to researchers at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) to build a globally inclusive musculoskeletal atlas of healthy tissues in collaboration with international partners.
The Ancestrally Inclusive Musculoskeletal Atlas Network is a global collaboration between multiple research institutes – the University of Oxford (UK), University of Bristol (UK), African Institute of Biomedical Science and Technology (Zimbabwe), University of Cambridge (UK) and University of Southampton (UK).
The network will collect tissues from under-represented communities spanning India, Zimbabwe, Turkey, The Gambia, Oman and Argentina. A cellular roadmap of ancestrally inclusive healthy musculoskeletal tissues will provide fundamental metrics to define the diverse tissues of the musculoskeletal system.
Prof Sarah Snelling, Associate Professor at NDORMS and chief investigator of the Ancestrally Inclusive Musculoskeletal Atlas Network, said: ‘The HCA is a generational resource that, when combined with future disease dataset, will accelerate our understanding of disease pathogenesis, revolutionise drug discovery and pave the way for the cellular evaluation of therapeutic strategies. It is vital that such a public good is representative of, and available too, all global populations.’
A flagship initiative of this network is to empower the data analysis within the low- and middle-income countries where tissue is being collected. The goal is to ‘train the trainers’ – helping to establish global centres of genomic research within these ancestrally underrepresented countries.
Dr Adam Cribbs, group leader in Systems Biology at NDORMS and computational lead for the project, said: ‘Developing computational infrastructure and support across our network will be key to empowering the future generation of scientists. This will lead to an increased representation of ancestrally diverse samples within the Human Cell Atlas project.’