Study uncovers why lupus patients have weaker response to COVID-19 vaccines

A recent study by Emory University researchers provides new insights into why the mRNA vaccines developed to fight COVID-19 in 2021 are less effective in patients with autoimmune diseases. By providing insights into the cellular processes behind that lessened protection, the new study published in Nature Immunology, highlights that lupus patients may require tailored vaccination strategies to enhance protection against COVID-19. The findings could also offer insights into the potential and limits of alternative ways to create immunity to COVID-19 through vaccines.

The study 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. 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."

Katia Faliti, PhD, lead author on the study, and instructor in Emory University's Department of Medicine

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 personalized approaches for each patient.

Study methodology

The study examines 79 lupus patients and 64 healthy individuals, focusing on B cells, the antibody-producing white blood cells vital for immune defense. In healthy individuals, mRNA COVID-19 vaccines create neutralizing 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 following COVID-19 vaccination. This increased frequency of DN2 B cells correlated with poor neutralizing 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."