Anti-CD20 Therapies Help Mount T-cell Response to COVID-19 Vaccines

Analysis may help in designing future vaccines for the immunocompromised

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with multiple sclerosis (MS) who are on therapies that deplete antibody-producing B-cells can mount an effective T-cell immune response to COVID-19 vaccination, a new study shows.

The findings suggest that the vaccines strongly activate other parts of the immune system that are helpful in fighting the virus, even in patients who failed to develop an antibody response.

“Our research makes a strong case for studying T-cell response to vaccines, rather than just antibodies, especially for immunocompromised individuals,” Roberto Alfonso, PhD, the study’s lead author from Tisch Multiple Sclerosis Research Center of New York, said in a press release from the institute.

The study, “Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies,” was published in Frontiers in Immunology.

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How do COVID-19 vaccines work?

Vaccines against COVID-19 can help to protect against serious illness by “teaching” the immune system how to fight the SARS-CoV-2 virus that causes the disease.

Immune proteins called antibodies, which are made by B-cells, are thought to be especially important for fighting off the virus because they can stick to it and prevent it from getting into cells.

Several MS treatments work by depleting B-cells. While these therapies are highly effective for preventing the progression of MS, they may also make patients more susceptible to infection and weaken the effectiveness of vaccines.

Some studies suggest other parts of the immune system can provide protection against infections, even in the absence of antibodies against the pathogens, but others have found conflicting results in the context of COVID-19.

To better understand these immune system responses, scientists at Tisch examined data from 43 MS patients who received a full course of COVID-19 vaccination a few months after their last course of B-cell-depleting therapies.

Participants had received either Ocrevus (ocrelizumab) or rituximab, which is not specifically approved for MS but is commonly used off-label for this indication. Among them, 27 had relapsing-remitting MS, while the other 16 had progressive forms of the disease.

All received a full course of one of the available COVID-19 vaccines: 22 got BNT162b2 (by BioNTech and Pfizer), 18 got mRNA-1273 (by Moderna), and three received Ad26.COV.2.S (by Johnson & Johnson).

Blood samples were taken from the patients about two months after finishing the vaccination course. Samples from 34 people without MS also were included as controls. The researchers noted that the control group consisted mainly of healthcare workers who were generally younger than the MS patients, and all but one person in the control group received the BNT162b2 vaccine.

Whereas all of the patients in the control group tested positive for antibodies that could block the SARS-CoV-2 virus from infecting cells, less than 1 in 4 (22.5%) of the MS patients were positive for blocking antibodies. A similar proportion of patients had any detectable antibodies against the virus.

Analyses of T-cells showed that, after exposure to a protein from the virus, T-cells from MS patients produced markedly higher average levels of interferon gamma and interleukin-2, two potent inflammatory signaling molecules that T-cells release to spur an immune attack against infectious invaders. Overall, 86% of MS patients had elevated levels of both molecules, compared with 73.5% in the control group.

T-cells from MS patients also divided more quickly in response to the viral protein than those from healthy controls.

The T-cell response did not appear to differ across MS types, the different B-cell-depleting MS treatments, or the different COVID-19 vaccines. The T-cell response also showed no apparent association with levels of anti-virus antibodies.

“Overall, the data presented here highlights a surprisingly strong active T-cell response” in people with MS on Ocrevus or rituximab, “even in the presence of a compromised humoral [antibody-driven] response to COVID-19 vaccination,” the researchers wrote.

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The team stressed that it’s impossible to draw clear conclusions about whether and how this T-cell-driven immune activity seen in the study might protect MS patients against infection in the absence of a working antibody-driven response, noting a need to track infection rates in patients on treatment to learn more. The small sample size and differences between the patient and control groups also were noted as study limitations.

Overall, this study “highlights the need to monitor vaccine-induced cellular response at the individual level, in addition to tracking antibody levels, for a better understanding of the benefits of current vaccination programs and the design of vaccinations in the future,” the researchers concluded.

Alfonso added: “Analyzing these patients’ T-cell response can lead to enhanced understanding of how they might respond to COVID-19 infection, data that could have important implications for how vaccines are designed for and administered to immunocompromised patients moving forward.”

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