Transmission electron microscopic image

Identification, Characterisation, and Optimisation of High-Affinity Antibodies Against SARS-CoV2

In this project crucial new understanding was developed of the adaptive immune responses elicited by two subsets of immune cell types in response to infection with the COVID-19 virus: virus-killing CD8+ T cells and antibody-producing B cells. Profiles were provided of these cells’ characteristics and functions during the acute infection phase and during the cells’ memory phase at both six- and twelve-months post-infection. 

The Need to Understand Humans’ Immune Response to the COVID-19 Virus

At the beginning of the COVID-19 pandemic there existed very limited knowledge of the precise ways in which the human immune system would react when it encountered the SARS-CoV-2 virus. This knowledge was essential to inform the clinical treatment of patients, and later, the vaccination and re-vaccination regimen. The interdisciplinary team of researchers, physician scientists and clinicians involved in this project developed crucial understanding that significantly contributed to filling this knowledge gap.

The overall aim of the project was to investigate human adaptive immune responses that occur during acute infection with SARS-CoV-2 and those immune system adaptations that have occurred six- and twelve-months after infection. The influence of mild and severe infection and subsequent vaccination on the cellular properties of the adaptive immune system were also examined. Specifically, attention was focused on two cell types of the adaptive immune system: CD8+ T cells, which kill virus-infected cells and B cells, which produce antibodies that bind to and neutralise the foreign antigen responsible for stimulating their production, in this case SARS-CoV-2.

Mapping Adaptive Immune Responses over 12 Months

During acute infection, both SARS-CoV-2 CD8+ T cells and B cells can become activated, expand and exert their respective immune functions.  After the primary infection is cleared, both cell types have the capacity to form long-lived memory cells. These memory cells can be rapidly activated during re-infection or vaccination, ensuring that an individual is less susceptible or even immune to a reoccurring infection with the same or a closely related pathogen.

The consortium succeeded in describing the physical characteristics of SARS-CoV-2-specific CD8+ T cells, as well as their frequency during the acute infection phase and memory phase at both six- and twelve-months. Differences observed between the SARS-CoV-2-specific memory CD8+ T cells formed following mild and severe COVID-19 infection indicate that processes which occur during the acute infection phase shape the future of the memory T cells.

The consortium also provided profiles of SARS-CoV-2-specific memory B cells, demonstrating that single clones of this cell type can have different fates with distinct functional phenotypes and characteristics. The findings also provided unique insights into the activities of so called ‘atypical memory B cells’ following infection and subsequent vaccination.

Potentially Wide-Reaching Implications

In sum, this project provided the scientific community with crucial new information about the trajectory of the human T and B cell adaptive immune response to SARS-CoV-2 and identified factors involved in shaping memory cells’ fate. These findings have potentially important implications for future pandemics and decisions that must be taken regarding prevention and control strategies. More generally, T and B cell memory formation play a role in many pathological conditions, including infection, chronic inflammatory diseases, cancer, autoimmunity and ageing and the findings of this project therefore have potential relevance across a broad spectrum of other conditions.

Banner image above: Transmission electron microscopic image of an isolate from the first U.S. case of COVID-19, formerly known as 2019-nCoV. The spherical viral particles, colourised blue, contain cross-sections through the viral genome, seen as black dots.

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Lead Researchers