MELODY: Study finds immunosuppressed people make antibodies after COVID-19 vaccination

Previous research has demonstrated that people with weakened immune systems, including those with autoimmune conditions like Scleroderma, are at increased risk of developing a severe infection after being exposed to Covid-19. Vaccinations and booster doses have been offered to immunosuppressed patients since the roll-out of the NHS vaccination programme in 2020. But how well do they work in people who have weakened immune systems?

How do vaccines work?

In most individuals, we know that COVID-19 vaccines stimulate the production of antibodies - complex molecules made by the immune system in response to infection, which help protect against and fight off the virus. Antibody levels are important because the higher a person’s antibody level, the better equipped they are to fight the infection.

However, previous studies, such as the MRC-funded OCTAVE study, have shown that people who are immunocompromised because of their medical condition or the medications they take might respond less effectively to COVID-19 vaccines. This means they are likely to produce lower levels of antibodies following a vaccination compared to ‘healthy’ controls.

The MELODY Study

At the end of 2021, doctors and researchers from Imperial College London, the Universities of Nottingham, Southampton, and Cambridge, the NHS, and other independent research organisations, came together to carry out the MELODY study. The study aimed to investigate how well vaccines protect people who have a weakened immune system from COVID-19 infection.

The team invited people who have had organ transplants, people with certain types of blood cancer, and people with rare autoimmune rheumatic disease such as Lupus, Vasculitis, Myositis, and Scleroderma to take part. People who had 3 or more COVID vaccines were asked to self-test for antibodies. 23,036 recruited individuals provided data to the study, 6,516 of which had rare autoimmune rheumatic diseases including Scleroderma. 29% of participants had received 3 vaccines at the time of their test, whilst 62% had received 4 vaccines, and 10% had received 5+ vaccines.

Participants received lateral flow immunoassay antibody tests to use at home, which required them to prick their finger and draw a small amount of blood to be tested for antibodies. They then reported their test result, and the team used the data to investigate how many participants had antibodies, and which factors might be linked to having or not having them after receiving at least 3 doses of the COVID-19 vaccine.

What did the study find?

The MELODY study showed that most immunosuppressed people do make antibodies after having the COVID-19 vaccination, meaning that the vaccine protects them from the viral strains they were vaccinated against. About 4 in 5 people that took part in MELODY had developed antibodies after having 3 or more vaccines. Antibodies were found in 77% of people who had an organ transplant, 79% of those with blood cancers, and 86% of those with rare autoimmune diseases like Scleroderma. 90.3% of people with Systemic Sclerosis that had 3+ vaccines tested positive for antibodies.

Unsurprisingly, those who received more doses of vaccine were more likely to have antibodies, along with those who were younger and those that had previously had COVID-19. On the other hand, some medications that weaken the immune system were found to reduce the likelihood of having antibodies. This included drugs such as mycophenolate, cyclophosphamide, and 'anti-CD20 therapies’ like Rituximab.

In addition to finding that the vaccine offers protection to those who are immunosuppressed, the study also demonstrated that patients self-testing for their antibody status is a reliable method of collecting data. The method could therefore enable assessment of immune responses and the protection afforded by vaccination in other cohorts, or for vaccinations for other diseases. The test could also be a useful tool to quickly identify people who do not have COVID-19 antibodies moving forward, which could enable high-risk patients to get quicker access to treatments.

As such, the MELODY study has demonstrated the value of vaccination for immunosuppressed individuals, and the importance of the UK vaccination programme. As a result of the findings of the study, the MELODY team has recommended that people with weakened immune systems continue to receive all vaccines and booster doses offered by the NHS.