Patients on Anti-CD20 Therapies Urged to Get COVID-19 Vaccine

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by Marisa Wexler MS |

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While people with multiple sclerosis (MS) taking anti-CD20 therapies do not mount a robust antibody response after getting vaccinated against COVID-19, the vaccines do strongly activate other parts of the immune system that are likely to be helpful in fighting the virus, a new study shows.

“The message from this study is clear — it is worthwhile for patients with MS receiving [anti-CD20] treatment to get a COVID-19 vaccine, which will prevent severe illness,” E. John Wherry, PhD, a professor at the University of Pennsylvania (Penn) and one of the senior authors of the study, said in a press release.

“Based on this body of evidence, we urge patients with MS receiving [anti-CD20 or] aCD20 treatment to get a COVID-19 vaccine if they haven’t already,” Wherry said.

The study, “Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy,” was published in Nature Medicine.

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Anti-CD20 therapies, known as aCD20, work by killing immune cells called B-cells. B-cells drive inflammation that damages the nervous system in MS, which is why aCD20 antibodies are thought to be effective as MS treatments.

To date, Roche’s Ocrevus (ocrelizumab) and Novartis’ Kesimpta (ofatumumab) are the only two approved aCD20 therapies for MS patients.

But rituximab is often used off-label as an anti-CD20 therapy in MS, and other aCD20 antibodies are currently being developed.

However, researchers note, B-cells also are important for protecting the body against infection, particularly by making antibodies — immune proteins that attack a specific target with high efficacy.

By binding to targets like the SARS-CoV-2 virus that causes COVID-19, antibodies can target the virus for destruction by immune cells. The Pfizer-BioNtech and Moderna vaccines for COVID-19 both work by inducing the production of antibodies that block the spike protein — which the virus uses to get into cells — and thereby prevent it from infecting cells.

These vaccines have been demonstrated to be safe and effective in clinical trials, but those trials largely did not include people with weakened immune systems, such as MS patients on aCD20 treatments.

Since aCD20 therapies work by killing B-cells, which make antibodies, it follows that people on these therapies will be less able to mount an antibody response after being vaccinated. However, whether other parts of the immune system might still respond to the vaccines — and, therefore, confer protection against COVID-19 — is not known.

To learn more, researchers from Penn’s Perelman School of Medicine now investigated how another kind of immune cell, called T-cells, fits into the COVID-19 vaccination picture. T-cells also are important for fighting viruses: among other functions, these cells can directly kill virus-infected cells.

“Often when determining if a patient mounted a proper response to an mRNA vaccine, we test for the presence of antibodies, but this method neglects an entire arm of a person’s immune response,” said Sokratis A. Apostolidis, MD, a fellow at Penn and study co-author.

“Measuring both antibodies and T-cell response gives us a more complete picture of a patient’s immune response,” Apostolidis said.

Blood samples were taken from 20 MS patients on aCD20 therapies at several time points before and after they were vaccinated for COVID-19. Antibody and T-cell responses were compared with 10 healthy individuals undergoing vaccination.

As expected, the MS patients had markedly diminished antibody responses, including fewer antibodies against the spike protein.

Of note, statistical analyses showed that, among MS patients, antibody responses were generally stronger among those who had gone a longer time after their last aCD20 dose before they were vaccinated. That’s likely because some of their B-cells were able to grow back, the researchers said.

“When the circulating B cell pool is repopulated with increased time since last aCD20 administration, vaccine-induced antibody responses approached those observed in healthy controls,” the team wrote.

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“Knowing that responses are weakest immediately following an anti-CD20 infusion, we can now advise patients to wait a number of months after their therapy to get a COVID-19 vaccine,” said co-author Amit Bar-Or, MD, a neurologist at Penn and also a study senior author.

In contrast to the diminished antibody responses, many subtypes of T-cells responded to the vaccine in the MS patients on aCD20 to a comparable extent as in the healthy controls, the study results showed.

In fact, the response for CD8 T-cells — the specific kind of T-cell that can kill virus-infected cells — was “more robust in patients with MS treated with aCD20 compared to healthy controls after the second vaccine dose,” the researchers reported.

The team noted that the CD8 T-cell response was especially strong in patients who did not make neutralizing antibodies.

“Overall, these studies provide strong evidence of immune priming by SARS-CoV-2 mRNA vaccines in patients with MS treated with aCD20. Although most of these patients do not generate optimal antibody responses, T cell priming … is largely intact,” the team concluded.

“Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20,” they added.

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