July 13, 2020

expert reaction to study looking at the immune response to COVID-19’s spike protein

A study, published in Nature Medicine, looked at the immune response to COVID-19’s spike protein.

Dr Al Edwards, School of Pharmacy, University of Reading, said:

“This study provides a detailed and comprehensive survey of the immune responses of a set of COVID-19 patients, compared with a small set of uninfected individuals. 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-CoV2 virus that causes COVID-19 disease.

“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. These diagnostic tests have been checked with hundreds and even thousands of samples. In an immunology research laboratory, hundreds of different responses can be measured much more precisely (but only for a few individuals). 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. Laboratories can also measure cells such as T lymphocytes. T cells can spot tiny chopped up fragments of a virus (called peptides) which makes it far harder for the virus to dodge immune defences. T cells can also coordinate and control antibody responses.

“What is vital about recent studies showing T cell responses is that we can start filling in all the gaps in understanding that can limit our responses to this new infection. For example, we knew that other milder coronavirus species cause a common cold (such as HKU1), but we didn’t know how similar or different our immune response to SARS-CoV2 was from HKU1. This more detailed understanding will be vital to develop effective vaccines, and improved diagnostic tests.

“This type of study was not designed to explore the most critical point which is how long people are protected from re-infection after recovery, and how strongly protected an individual is by these complex immune responses. However, the human immune system is a powerful and sophisticated defence and it has protected us from many other viral infections. It will take longer, clinically focussed studies of rates of re-infection – many of which are already ongoing – to work out how well our immune system protects us from this new virus. When these longer studies start to provide answers to these most pressing questions, the underlying immunology can be used to understand and make use of future findings.”

Prof Mala Maini FMedSci, Wellcome Trust Senior Investigator at University College London, said:

“This is an interesting and elegant study. Unlike many studies just looking at antibodies, this one looks at other important players: memory B cells and a type of T cell (T-follicular helper cell) that is specialised to help B cells make antibodies to the spike of COVID-19 efficiently.

“The novelty is showing that all these players could be detected in the blood one month after COVID-19 infection indicating that key protective immune responses can be generated in natural infection and have the potential to be boosted.

“Only a small group of adults who had mild infection were studied and there was no follow-up beyond one month. The blood is only a proxy measure of the cellular immune responses going on in lymph nodes and lungs.

“It will be important to study these cellular players alongside detailed antibody studies in a larger group of individuals followed for longer to understand more about their use as correlates of protection for biomarkers or vaccine targets.”

Commenting on both the study in Nature Medicine and also a preprint by Seow et al (there is also an SMC roundup on this preprint)

Prof Charles Bangham FRS FMedSci, Chair of Immunology, Imperial College London, said:

“The study by Juno et al is an important reminder that the T cell response is a critical component of an effective anti-viral immune response.  T cells are necessary to enable antibody production, and T cells can also directly kill virus-infected cells.  It is often stated that an effective vaccine against SARS-CoV-2 must elicit neutralising antibodies.  But neutralising a virus in the test tube is studying only one way that antibodies can protect against the infection in the body.  It is therefore important to measure not only the neutralising antibody, but also the total quantity of SARS-CoV-2-specific antibodies as the total virus-specific antibody amount is sometimes a better indicator of protection.

“Seow et al (https://doi.org/10.1101/2020.07.09.20148429) carried out a careful longitudinal study of the antibody response to SARS-CoV-2 for up to 94 days after the onset of symptoms, in 65 people with PCR-confirmed infection.  They show that the amount of in vitro neutralising antibody declines within a few months to near baseline in people who recovered from COVID-19.  But not all of the types of antibody declined so quickly, and these individuals may be left with some protection against re-infection.  These results are consistent with previous evidence that the immune response to endemic coronaviruses – which can cause the common cold – wanes within months of infection, and raises the question how long protective immunity lasts.  The authors also note that ‘…the role T-cell responses generated through either infection or vaccination play in controlling disease cannot be discounted in these studies and defining further the correlates and longevity of vaccine protection is needed’, reinforcing the implications of the study by Juno et al.

“The most effective anti-COVID-19 vaccine is likely to elicit both neutralizing antibodies, and a high total antibody titre, and a strong T cell response.”

Prof Danny Altmann, British Society for Immunology spokesperson and Professor of Immunology at Imperial College London, said:

“Studies of SAR-CoV-2 T cell immunity are the vital, next step in assessing who has immunity, how long it lasts and which tests might predict protection. This team have looked at responses to the virus Spike antigen by a subset of white blood cells called T follicular helper cells. These are the kind of T cells that talk to and stimulate the cells that produce antibodies. The team find that detection of these T cell responses is a good predictor of immunity. A key priority now is to roll-out T cell assays more widely, to understand if these responses offer more durable immunity than antibody and most importantly, to be sure whether this is a true correlate of protection.”

‘Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19’ by  Juno et al was published in Nature Medicine on Monday 13^th July 2020.

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.