Describing immunity to COVID-19 – a key to unlock vaccines and treatments

Immune systems are complex and immune responses vary from person-to-person. If researchers can unlock the mysteries behind how the immune system responds to certain invaders, it can be the key to effective vaccines and immunotherapies.

Kent Laboratory

University of Melbourne Professor Stephen Kent’s laboratory at the Doherty Institute has set out to try to understand as much as they possibly can about how the immune system behaves when faced with COVID-19.

Much of the work was led by Dr Jennifer Juno, a postdoctoral researcher in the Kent Lab.

Dr Juno and the team have looked at what happens to immunity levels four months after COVID-19 infection, describing the immune response to the spike protein (the protein that COVID-19 vaccines target) and immunity to other coronaviruses.

The first big breakthrough for the group came in July 2020, when they uncovered how a crucial component of the immune system responds to the spike protein of SARS-CoV-2.

3D Rendering Covid-19 SARS-Cov-2 Viruses Model Spike Proteins
3D Rendering T-Cells and Antibodies Attacking Covid-19 Coronavirus Spike Proteins
3D Rendering Covid-19 SARS-Cov-2 Viruses Model Spike Proteins
3D Rendering T-Cells and Antibodies Attacking Covid-19 Coronavirus Spike Proteins

Coronavirus particles have a corona (crown) of proteins resembling spikes, which enables the virus to attach and enter cells in humans. The spike protein is crucial for inducing neutralising antibodies to protect from reinfection.

“We were particularly keen on looking closely at B and T cells and how they respond to the spike protein,” explains Dr Juno. “B cells are responsible for producing the antibodies that recognise SARS-CoV-2, while T cells play an important role in supporting the development of the B-cell response.”

The team looked at a cohort of samples from people who experienced mild-to-moderate COVID-19, as that’s the kind of immune response that mimics what a vaccine might induce.

“We found that those who showed strong neutralising antibody activity had a robust B-cell response, but most surprisingly, we also found that a particular subset of T cells, called T-follicular helper cells, was a great predictor of an effective immune response,” says Dr Juno.

Kent Laboratory Zoom meeting

Kent Laboratory meeting during lock down

Kent Laboratory meeting during lock down

In addition to COVID-19, the researchers also looked at other circulating coronaviruses that cause the common cold in an effort to understand what would predict the neutralising response to SARS-CoV-2 and to better understand long-term immunity to coronaviruses.

“We found that almost all adults show evidence of both antibody and T-cell responses to these viruses, although often at relatively low levels. This provides evidence that the immune system can remember encounters with coronaviruses, even if they only cause mild illness,” explains Dr Juno.

One of the million-dollar questions on everyone’s mind as COVID-19 vaccines rollout globally is how long vaccine-induced immunity will last.

Research published in Nature Communications by the Kent Lab does provide a clue.

“Data continues to emerge about the impact of vaccines on immunity to the virus, however, a striking observation from our study was that over the four months we tracked patients following COVID-19 infection, the number of B cells recognising the spike protein increases in almost all of them, regardless of how severe their disease was,” says Dr Juno.

“This is interesting because our work and other recent studies suggest these B cells are continuing to accumulate and potentially evolve over time. That should be useful for protection in the event of another exposure in the sense that those ‘memory’ cells should be able to be activated again.”

All of this knowledge is important for future studies of COVID-19 vaccine responses and the understanding of immunity to other respiratory viruses.

Dr Juno and her team’s work is supported by the National Health and Medical Research Council (NHMRC), the Medical Research Future Fund (MRFF) and the Victorian Government.

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