Outlines

A research group including Yuta Yamaguchi (then a doctoral student, currently the Assistant Professor in the Department of Pharmacology at the Institute of Science Tokyo), Saori Amiya (then a doctoral student, currently a chief physician in the Department of Respiratory Medicine at Ikeda City Hospital), Assistant Professor Yasuhiro Kato, and President Atsushi Kumanogoh (Department of Respiratory Medicine and Clinical Immunology) from the Graduate School of Medicine of the University of Osaka, tracked the changes in neutralizing antibody titers in patients with autoimmune diseases (connective tissue disease) after receiving an mRNA vaccine against the new coronavirus disease 2019 (COVID-19) up to five doses. As a result, the changes in neutralizing antibody titers were divided into three groups, and there was a group whose antibody titers did not increase sufficiently even after repeated vaccination. Furthermore, by measuring serum cytokines and analyzing immune dynamics, rather than just observing the effects of the medication or disease, the researchers found that in the group whose antibody titers did not rise sufficiently, inflammation within the body may have affected the effectiveness of the vaccine.

From the results of previous research, it had been thought that repeated vaccinations might reduce the effects of medication and diseases.

However, the results of this study suggest that even after multiple vaccinations, the effectiveness may still be affected by the medication or the patient's own immune dynamics. This is believed to be an extremely important research result in developing optimal vaccine strategies tailored to the condition of each patient and is expected to be extremely useful when considering COVID-19 prevention measures and treatment strategies for autoimmune diseases.

Figure: Changes in neutralizing antibody titers up to five vaccinations

Credit: Yasuhiro Kato

Research Background

It has been reported that patients with autoimmune diseases have higher risks of developing severe symptoms from COVID-19 than healthy individuals, so it is essential to prevent infection and the disease from becoming severe through vaccination. Autoimmune diseases and their medication may weaken vaccine-induced immune responses, so it is very important to clarify the factors that affect vaccine’s efficacy.

In 2022, the research group presented a paper tracking the progress of antibody titers up to about one year after two doses of the vaccine and examining the effects of disease and medication. As an advanced study, the researchers have examined the effects of repeated vaccination.

Research Contents

In this study, blood samples were collected from patients currently receiving treatment at the University of Osaka Hospital, and changes in neutralizing antibody titers against COVID-19 before and after receiving mRNA vaccination were analyzed. Patients were then divided into three groups based on the pattern of antibody titer progression: 1) those whose antibody titers increased sufficiently after two vaccinations, 2) those whose antibody titers increased after three vaccinations, and 3) those whose antibody titers did not increase even after three vaccinations.

Use of abatacept is a factor that makes patients more likely to be assigned to groups 2 and 3, and factors that make patients more likely to be assigned to group 2 included advanced age, use of mycophenolate mofetil, ANCA-associated vasculitis, and rheumatic disease. On the other hand, patients with systemic lupus erythematosus were less likely to be assigned to group 2. Patients in group 3 had higher levels of inflammatory cytokines in their blood compared to the other groups, suggesting that the patient's immune dynamics may be affecting the effectiveness of the vaccine.

Social Impact of the Research

This study clarified that antibody titers are particularly difficult to increase with mRNA vaccination in patients who are using abatacept or who have high levels of inflammatory cytokines in their blood. In patients whose disease is stably controlled, the effectiveness of the vaccine may be improved by discontinuing of medication for a certain period before vaccination or by carefully considering its timing. The results of this research are expected to be efficient in considering vaccine administration plans and infection prevention measures tailored to each patient's condition, medication, and age.

Notes

The article, “Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis,” was published in a scientific journal of Vaccine at DOI: https://doi.org/10.1016/j.vaccine.2025.127771.