Australian research provides COVID-19 vaccine hope

The Doherty Institute study, published in Nature Medicine, uncovered how an important part of the immune system responds to coronavirus, which could help assess how strong of a neutralising antibody response a vaccine might induce.
 
Recent studies have suggested that antibody immunity from natural infection may not be long lasting, which has also raised concerns about the ability to produce a long-term vaccine to protect against coronavirus.
 
However, antibodies are not the body’s only form of defence against viruses, and the new research has shown the response of B and T cells is a crucial predictor for how well the immune system responds to a coronavirus infection.
 
The research achieved this by investigating the ‘crown’ of proteins found on coronavirus particles, which resemble spikes and enable the virus to attach and enter cells in humans.
 
According to the institute, theses spikes are also crucial in inducing neutralising antibodies to protect from re-infection, as they not only bind to the viral spike protein, but also prevent it from being able to attach to and enter human cells.
 
A major focus of the research was investigating how B and T cells respond to a coronavirus spike, as 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.
 
Lead author Dr Jennifer Juno, a postdoctoral researcher at the Doherty Institute, said the team looked at people who had recovered from COVID-19 and mostly experienced mild or no symptoms, since that kind of immune response 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,’ Dr Juno said.
 
‘We have previously demonstrated through influenza research that B cells are key to mounting an effective immune response to influenza, and we also know that T-follicular helper cells specifically help B cells to make antibodies.’
 
Associate Professor Al Edwards, from the University of Reading’s School of Pharmacy, said the findings provide ‘a detailed and comprehensive survey of the immune responses of a set of COVID-19 patients’ that had previously been lacking.
 
‘The importance of this study is that it starts to unpick the details of all the diverse components of our immune response against the SARS-CoV-2 virus,’ he said.
 
‘There has been a lot of discussion about diagnostic antibody tests for COVID-19. However, these certified diagnostic tests are currently designed to detect one single antibody response, and not to quantify it.
 
‘By measuring the levels of different responses, we can build up a better picture of exactly what viral components our body is good at attacking.’
 
The Doherty Institute team is hopeful the ‘immune parameters’ it has identified can be applied to clinical vaccine trials, because generating a strong neutralising antibody response is an important goal for SARS-CoV-2 vaccines.
 
‘Now we know how the immune system responds to the spike protein, and we have these biomarkers or predictors of what elicits a good or poor immune response to COVID-19, we can look at the vaccine candidates and see what will offer the best protection,’ Dr Juno said.
 
What do the findings mean for herd immunity?
In addition to COVID-19, the researchers also looked at circulating coronaviruses that cause the common cold in an effort to understand what would predict the neutralising response to SARS-CoV-2. These findings were consistent with what was described in the immune responses of other people who had recovered from COVID-19.
 
Some researchers have suggested existing immunity to colds caused by other coronaviruses, among other ‘immunological dark matter’, could also afford a level of protection against COVID-19. If true, it would potentially make herd immunity achievable with an infection rate of around 20%, rather than the 60–70% level that is commonly cited.
 
This theory has also been fuelled in part by recent drops in daily case numbers and deaths recorded in Sweden – which has deliberately pursued a herd immunity strategy and avoided major social distancing restrictions – despite reports indicating it had overestimated how many people had achieved natural protection against COVID-19 through infection.
 
However, while the new study shows that high titres of antibodies and memory T cells to human coronavirus (HKU1) are present in those that have recovered from COVID-19, Monash University biomedical scientist Dr Emily Edwards told newsGP it is still not known whether these antibodies can neutralise SARS-CoV-2.
 
‘We also don’t know whether T cells that recognise common coronaviruses can eliminate COVID-19-infected cells,’ she said.
 
‘Although it is a possibility that these responses could protect against COVID-19, the high incidence and severity of SARS-CoV-2 infection implies that this is not the case.
 
‘If it were it is unlikely we would have a global pandemic on our hands.’
 
Dr Edwards said there is thus still ‘limited information’ to suggest that pursuing herd immunity would be an efficient strategy to control COVID-19 infection.
 
‘Although T cells that recognise SARS-CoV-2 have been identified in individuals with no exposure to the virus, it is unclear whether these cells can recognise and eliminate virally infected cells,’ she said.
 
‘In particular, killer T cells are known to play a crucial role in the control of viral infection; however, their role in COVID-19 clearance and disease development remain unresolved.
 
‘This article from the Doherty Institute beautifully illustrates that COVID-19-recovered patients possess T cells that recognise SARS-CoV-2 and other coronaviruses. But whether these cells cross-recognise other viruses is unclear, or whether they provide protective immunity is unclear.
 
‘Due to the catastrophic nature of this virus globally, the danger of assuming that a 20% infection rate will confer herd immunity is risky, in my opinion.’
 
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B cells coronavirus COVID-19 herd immunity immunity T cells vaccines