Recent reseearch has provided new insights into why the mRNA vaccines developed to fight Covid-19 in 2021 are less effective in patients with autoimmune diseases, suggesting these individuals may need tailored vaccination strategies to boost their protection against the virus.
The findings by the team from Emory University could also offer insights into the potential and limits of alternative ways to create immunity to Covid-19 through vaccines for these patients, reports MedicalXPress.
The study, published in Nature Immunology, provides the first evidence that vaccine-induced responses generate a novel type of memory B cell. These newly discovered cells could contribute to booster responses and infection protection. However, their role in ensuring long-term immunity or offering an advantage against future infections remains to be clarified.
Systemic Lupus Erythematosus (SLE) – lupus for short – is a chronic, painful and debilitating disease in which the antibodies produced by the immune system mistakenly attack the body’s own tissues. When mRNA vaccines began to be used against Covid-19 in 2021, it became important to understand whether and why they might give less protection to vulnerable subjects, such as those with lupus.
“These findings are important because they help us understand how immune responses from vaccines develop and last in people with autoimmune conditions like lupus,” said Katia Faliti, PhD, lead author on the study, and an instructor in Emory University’s Department of Medicine.
“By examining a diverse group of lupus patients who have never been exposed to Covid-19 viral infections, we explore both antibody-based and cellular-based immunity. We identify key factors that contribute to strong vaccine responses, as well as those that may limit protection.”
The researchers believe their findings will have broad application to autoimmune diseases with defective B cell components beyond just lupus, while providing more insights into personalised approaches for each patient.
Study methodology
The study examined 79 lupus patients and 64 healthy individuals, focusing on B cells, the antibody-producing white blood cells vital for immune defence. In healthy individuals, mRNA Covid-19 vaccines create neutralising antibodies and establish immune memory, a cellular process that allows the body to respond to later attacks of pathogens more quickly and effectively.
In contrast, the researchers found that mRNA Covid-19 vaccines in lupus patients were less effective in creating the anti-spike immunity that provides protection in healthy subjects.
While virtually 100% of healthy control subjects who received the vaccine produced B cells that attacked the spike protein – the protruding part of the Covid-19 virus that allows it to spread infection – a portion of lupus subjects (about 10 to 30%) generated B cells that failed to attack the spike at all.
In their paper, the researchers discovered that a pathway involving a distinct subset of B cells, known as DN2 B cells, previously linked to pathogenic autoimmune responses, was significantly more frequent in lupus patients than in healthy ones after Covid-19 vaccination.
This increased frequency of DN2 B cells correlated with poor neutralising antibody response, the process that normally allows antibodies to stop a pathogen from infecting the body, in lupus patients.
“We previously showed that DN2 B cells are associated with lupus disease and severity, particularly in women of black ancestry,” said Iñaki Sanz, MD, professor of immunology in the School of Medicine and senior author of the study.
“Now we’ve discovered evidence for which vaccine-mediated DN2 B cell activations persist over time, even more than six months after vaccinations, when immune memory is formed, and make up a much larger fraction of the anti-Covid-19 persistent memory in people with lupus.”
Study details
Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE
Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam et al.
Published in Nature Immunology on 12 November 2024
Abstract
Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralisation potency and breadth. We also observed a sustained anti-spike response in IgD−CD27− ‘double-negative (DN)’ DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.
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Covid jab response reduced in lupus patients – Johns Hopkins study
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