Why COVID-19 Vaccines Are Less Effective in Lupus Patients

Immunocompromised people don’t develop as robust a response to vaccines as immunocompetent individuals. This is the case for the COVID-19 vaccine, but the reasons why aren’t well understood.

Researchers from Emory University are closer to an answer with their study on vaccination in lupus patients. Lupus patients have compromised immune systems either because of the disease itself or because of the immunosuppressive drugs used to treat the disease.

In this work, they compared the B cell response of 79 lupus patients and 64 healthy people after receiving the COVID-19 mRNA vaccine. B cells are the immune cells that produce antibodies (ex: against the SARS-CoV-2 spike protein) which make them a good subject of study. 

In lupus patients, the researchers noticed that the B cell response is not as efficient in creating antibodies against SARS-CoV-2. In healthy individuals, nearly all subjects produced B cells that attacked the virus while 10-30% of lupus patients generated B cells that did not attack. 

One of the culprits behind this difference is a pathway that involves “double negative” B cells called DN2. These cells were more prevalent in their vaccinated lupus cohort than vaccinated individuals without lupus. These cells, which were previously linked to autoimmune responses, also correlated with a poor neutralizing antibody response to the spike protein.

The knowledge gained from this work could help inform vaccine strategies in the future for immunocompromised individuals that can better fine-tune vaccine dosage and timing around immunosuppressive therapy.

Citation:

Faliti, C. E., et al. (2025). Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE. Nature immunology, 26(1), 131–145. https://doi.org/10.1038/s41590-024-02010-9