T-cells help protect against risk of COVID-19 infection in MS: Study
No increase seen post-vaccine for patients on B-cell depleting therapies
The use of B-cell depleting therapies does not increase the risk of an infection with COVID-19 among people with multiple sclerosis (MS) who have been vaccinated, according to the findings of a new study by U.S. researchers.
While such treatments did compromise the body’s ability to develop antibodies against the virus that causes COVID-19, a greater post-vaccine response from immune T-cells — types of white blood cells that play a key role in the body’s immune system — appeared to make up the difference, the study found.
“Together, our results establish a critical role for T cell-mediated immunity in antiviral protection,” the researchers wrote.
The study detailing these findings, titled “Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy,” was published in the journal npj Vaccines. The work was funded in part by Novartis, which markets the B-cell depleting therapy Kesimpta (ofatumumab).
Use of B-cell depleting therapies became a concern during pandemic
B-cell depleting therapies, or anti-CD20 antibodies, are a class of MS treatments that work, as their name indicates, to lower levels of B-cells in people with the neurodegenerative disease. These antibody-producing immune cells are believed to be central to the inflammatory attacks that damage the brain and spinal cord in MS.
However, B-cell activity is also important for developing immunity in response to vaccines, and the use of such therapies could compromise how effectively that response is mounted. This became a particular concern during the COVID-19 pandemic, the researchers noted.
A main class of COVID-19 vaccines is mRNA vaccines, which deliver a template molecule encoding for an important viral protein called Spike. The body uses that blueprint to produce Spike and learn how to attack it as a harmful invader.
This involves the production of anti-Spike antibodies from B-cells — called a humoral response — as well as activity from immune T-cells, known as the cellular response. If the body is later exposed to SARS-CoV-2 — the virus that causes COVID-19 — these cells will be equipped to recognize and eliminate the infection.
In this study, a team led by scientists at the Columbia Multiple Sclerosis Center and Center for Translational & Computational Neuroimmunology in New York, explored in greater detail how T- and B-cell responses to mRNA vaccines are affected by the use of anti-CD20 antibody therapies. The researchers looked at therapies such as Kesimpta, Ocrevus (ocrelizumab), and rituximab, which is sometimes used off-label to treat MS.
Blood samples were collected from 43 people with MS who were taking B-cell depleting therapies and 58 patients who were not. None of them had a history of COVID-19 infection. The samples were taken between four days and more than a year after a standard two-dose course of a COVID-19 mRNA vaccine.
Similar low risk of COVID-19 seen for patients regardless of therapy use
As expected, people on B-cell depleting treatments had significantly lower B-cell levels than those not on such medications. These patients also showed a compromised humoral response after vaccination, with significantly lower levels of antibodies against the virus.
According to the researchers, individuals not using B-cell depleting therapies generated an antibody response that declined within seven months of vaccination — as is usually seen in the general population. People on these treatments never mounted such a response to begin with, and antibodies were generally undetectable or negligible at any time.
Importantly, however, the participants on B-cell depleting therapies showed an enhanced cellular response mediated by T-cells after vaccination. That finding has been reported in other studies.
While the total numbers of T-cells did not vary between the groups, patients given anti-CD20 antibodies had significantly higher rates of Spike-reactive T-cell subsets compared with the control group. This was particularly pronounced in people who received Kesimpta.
The response was sustained over time, and could be detected in some people even more than a year later, the researchers found.
“Together, these findings demonstrate that BCD [B-cell depleting] participants develop long-lasting cellular immunity despite negligible humoral immunity,” the team wrote.
[Accumulating data] provide compelling evidence for the protective role of T cell immunity to SARS-CoV-2 [the virus that causes COVID-19] in humans.
A larger analysis including participants from this study and others showed that a third booster dose of an mRNA vaccine could help enhance B-cell responses, although those on B-cell depleting therapies continued to have lower antibody responses compared with those on other treatments. The third dose, however, had less of an effect on the already strong T-cell responses, the analysis found.
Importantly, people who did or did not use anti-CD20 antibodies were similarly protected against COVID-19 infection. Fewer than 10% of people in either group reported an infection in the nine months after they completed a two-dose vaccination series. All reported infections were mild and none required hospitalization.
“Despite the absence of humoral immunity in BCD participants, they experienced similar clinical protection from symptomatic infection as non-BCD participants,” the researchers wrote, noting that accumulating data “provide compelling evidence for the protective role of T cell immunity to SARS-CoV-2 in humans that may also extend to other respiratory viruses.”
While B-cell depleting therapies are also used for other indications, including for treating certain cancers, the authors noted that whether or not similar immune responses are observed in these groups is not established.
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