New research shows that multiple sclerosis patients undergoing anti-CD20 treatment – which depletes the B-cells that contribute to the MS attacks – are able to mount robust T-cell responses to the mRNA COVID-19 vaccines, despite having a muted antibody response to the vaccines.

Because B-cells are responsible for antibody production, patients’ ability to produce antibodies preventing the virus from entering and infecting a person’s cells is significantly muted when the B-cells are depleted with anti-CD20 treatment. But the same patients are nonetheless able to mount very good responses of the second protective arm of their immune system, which uses T-cells to eliminate cells once infected (thereby preventing viral spread to other cells), according to new research from the Perelman School of Medicine at the University of Pennsylvania.

The study measured both the antibody and T-cell responses in 20 patients with MS who were undergoing anti-CD20 treatment, compared to those in a group of healthy controls. None of the participants in the study had prior clinical signs or symptoms of COVID-19. Researchers analyzed cell samples five times over the study period: prior to the first vaccine dose, 10-12 days following the first vaccine dose, prior to the second vaccine dose, 10-12 days following the second vaccine dose, and 25-30 days following the second vaccine dose.

All healthy control subjects generated both antispike and antireceptor-binding domain antibodies following the first dose of mRNA vaccine, and the level of antibodies increased further after the second dose. However, in patients with MS, the antibody response was far more varied. By 30 days after the second vaccine dose, 85 percent of participants developed anti-spike antibodies, and 50 percent mounted anti-RBD responses. For those subjects who did have detectable antibodies, the magnitude of response was generally lower, and the response was delayed compared to the control group.

The timing of a patient’s last anti-CD20 infusion – typically administered every six months – played a significant role in the immune response mounted. Patients with MS with higher percentages of circulating B-cells prior to the vaccine had more robust antibody responses to the vaccine.

Researchers found that patients who had undergone anti-CD20 treatments had T-cells that responded similarly to vaccination as healthy control subjects. Patients who underwent anti-CD20 therapy generated robust T-cell responses to the COVID-19 vaccination. This observation reveals that even without circulating B-cells, the COVID-19 vaccine effectively primed patients’ immune response to the virus.

The researchers note that because of the limited antibody responses mounted by patients receiving anti-CD20 treatments, they might not be able to neutralize the virus as quickly before it infects other cells, which could result in them being contagious carriers of the virus for a longer period of time.

The findings were published in the journal Nature Medicine.