Could I be at risk? What we know so far about immune responses to the COVID-19 vaccination in those with weakened immune systems

As the UK strives to give every adult their COVID-19 vaccinations, what do we know about their effectiveness in protecting those with weakened immune systems such as some individuals with scleroderma?

Could I be at risk? What we know so far about immune responses to the COVID-19 vaccination in those with weakened immune systems

The scale of this years’ rollout of the COVID-19 vaccine is unprecedented, a true ‘first’ in medical history. At the time of writing almost 85m vaccine doses have been given in the UK; around 90% of adults have received their first dose of vaccine and 70% their second dose. With this impressive milestone under our belt, attention is now turning towards autumn and the booster program.

But for those in our community with systemic sclerosis, particularly those taking certain medicines which suppress the immune system (immunosuppressants), there may be concerns about the effectiveness of the vaccines and the level of protection they offer.   

Vaccines: immune memory in the absence of infection

Currently, the MHRA have ‘authorized’ four vaccines for emergency pandemic use in the UK. These are the mRNA vaccines from Pfizer and Moderna and the viral vector vaccines from Astra Zeneca and Janssen (Johnson and Johnson). Whilst these vaccines are subtlety different (find out how) they all have the same overarching aim; which is to trick the body into believing it has been infected with SARS-CoV-2, the COVID-19 virus in order to teach the immune system how to fight the COVID-19 virus should it be encountered in the future.

Vaccines are targeted towards our ‘adaptive’ immune response. This type of immunity represents lifelong learning and is honed and refined throughout our lives as we encounter more and more disease-causing organisms. It is orchestrated by two types of white blood cells known as T cells and B cells.

When we become infected with a virus like SARS-CoV-2 the immune system scrambles; T cells recognize virally infected cells and, dependent on their job title, do one of two things. Killer T cells are the assassins of the immune system recognizing virally infected cells, killing them in a targeted and efficient manner. Another type of T cells called ‘helper T cells’ ensure the right type of immune responses are generated to clear the infection. Helper T cells act like a conductor providing cues to killer T cells and B cells to tell them how to act. This latter type of cell, the B cell, churn out antibodies, specialized proteins released into the blood which are specific to a unique disease-causing organism. Antibodies recognize and bind to the COVID-19 viral spike protein, ‘neutralising’ it and preventing the virus from entering human cells.

Once the infection is cleared, memory T cells and B cells enable the immune system to remember these past encounters. This ‘long-term memory’ response in the absence of infection is the goal of vaccination.   

Safety and efficacy of the COVID-19 vaccines

The current COVID-19 vaccines are the fastest vaccines in medical history to be developed: the fastest (Pfizer) having been developed, trialed, and authorized for pandemic usage, well inside of 12 months. This speedy work was in part due to a wealth of research which has been carried out on the back of other pandemic ‘false alarms’ like SARS and MERS, and the role that international governments played through providing support to help ’de-risk’ the early stages of vaccine development, allowing this work to proceed at pace. Around the world, thousands of people selflessly volunteered to participate in the rapid clinical trials of these vaccines to help ‘get us out of the pandemic quicker’. People with chronic underlying conditions like inflammatory and autoimmune conditions were usually excluded from these trials. Whilst these ‘emergency authorized’ vaccines have been used globally in those with autoimmune conditions and proved to be well tolerated, less is known about the overall effectiveness of these vaccines in these individuals compared to the general population.

Autoimmune disease and the role of immunosuppression

People with autoimmune rheumatic diseases like systemic sclerosis have immune systems on overdrive. Their B cells busily produce ‘autoantibodies’. These are antibodies directed against ‘self’, or their own body, and drive the various aspects of the condition. In this case, ‘immunosuppressant’ medications like high dose steroids such as prednisone, or other treatments like methotrexate, rituximab, mycophenolate mofetil, azathioprine, cyclophosphamide and cyclosporine are often prescribed. These all serve to dampen down elements of an over-active immune system.  Unfortunately, these medications may weaken the broader immune response, making patients more prone to infection and perhaps, reduce their immune responses to vaccination.  

How might immunosuppressants affect a person’s immune responses?

Much of our knowledge, up until now, has come from studying recipients of solid organ transplants. Transplant patients are dependent on a strong cocktail of immunosuppressant drugs to prevent rejection of their transplanted organ. This regimen is likely to be much stronger than any immunosuppression given to a patient with systemic sclerosis. It is already known that the weakening effect of these medications on the immune systems of transplant patients can lead to lower immune responses to other vaccines like influenza and hepatitis B. Unsurprisingly, the same was found during studies of the effectiveness of the COVID-19 vaccine. A study of 658 organ transplant patients who received mRNA COVID-19 vaccines found that half of the recipients had detectable anti-COVID antibody levels 28 days after their second dose. This suggests that the remaining half of those vaccinated did not mount an adequate immune response post-vaccination.

Immune responses in those with autoimmune conditions

But what about the situation for those who are immunosuppressed through medications being taken for autoimmunity? A few small studies have been carried out in people with autoimmune rheumatic diseases, but these are mostly limited by the fact that they have only reported the immune responses made after the first dose of vaccine.  In general, these studies show that people with autoimmunity have reduced antibody responses after their first dose of vaccine with one study showing that anti-COVID-19 antibody levels were significantly lower in those taking rituximab or mycophenolate compared to the general population. Suggesting that people taking these medications might be at a greater risk of infection between first and second doses.

A small body of work has reported on the responses after the second dose through a study funded by Public Health England, which as part of the analysis examined the responses of those with weakened immune systems through immunosuppression. After the first dose in the 132 people studied, reduced antibody responses were noted after the first vaccine dose. A smaller group of 39 people were studied after their second dose of vaccine, where 97% of these immunosuppressed individuals had an antibody response. This response is comparable to what is seen in people with ‘normal’ immune systems. This is clearly encouraging, but should be approached with caution, since this is a very small group of individuals, and because of this we cannot draw any robust conclusions regarding the influence of different types of medicines and particular conditions on the immune response generated.

What is being done to better understand the risk? 

The above studies were relatively small and just used antibodies as a readout to measure the effectiveness of vaccination. But antibodies are only one part of the response to viruses, T cells are key responders and influence antibody responses, so arguably an understanding of this aspect of the immune system in the immunosuppressed versus the broader population may be of greater relevance. However, in contrast to antibodies which can be easily measured in the blood, understanding and measuring T cell responses is much more complicated. Fortunately, there are some larger studies in progress that should shed some light on this area:

1, The OCTAVE study

In the UK, the Medical Research Council (MRC) have funded the multi-centre ‘OCTAVE’ study which will evaluate the immune response to COVID-19 vaccines in around 5,000 patients with impaired immune systems through cancer, transplants and inflammatory disease. Taking place at six UK sites, researchers will use state of the art technologies to analyse an array of immune responses generated to the vaccine in people, including the effects of different types of medications. As a follow on, a second project ‘OCTAVE DUO’ which will start this month, will look at how immunity is best boosted in these patients.


    The Coalition for Epidemic Preparedness Innovations (CEPI) in partnership with a consortium of Norwegian health organisations are also planning a similar study. The responses of 6,000 patients who have received two doses of either the Moderna or Pfizer vaccines will be studied and compared to those of 10,0000 ‘healthy’ volunteers. Researchers will analyse T and B cell responses in participants to vaccination, those with limited or no response to the vaccine will be given a third booster dose with the effectiveness of this studied.

    Hope for the future?

    If immune responses are found to be significantly reduced in people with autoimmune rhematic diseases like scleroderma, some hope comes from another small study of 30 transplant patients, which showed that a third vaccine booster dose could increase antibody levels, converting the ‘low’ antibody responders into ‘high’ responders.

    The work being carried out across the medical field is of utmost importance, the findings will empower those who are clinically extremely vulnerable and help them to understand their level of infection risk after vaccination. The research will hopefully enact positive change within the healthcare system and will dictate vaccination policy in response to COVID-19 and beyond. We will update you as the findings of OCTAVE and the CEPI sponsored studies are released. In the meantime, we encourage you to speak to any loved ones eligible for vaccination who have not yet been vaccinated and encourage them to do so. Vaccination serves to protect others in society, such as the clinically vulnerable, from infection as well as the person vaccinated. Our recently updated COVID pages continue to offer help and support and you may contact us with any questions you may have.