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Response to COVID vaccines in people with MS treated with B cell depleting therapies

  • People treated with B cell depleting therapies for multiple sclerosis (MS), such as Ocrevus and Kesimpta, produce lower levels of protective antibodies in response to COVID-19 vaccines.
  • However, there are two major arms of the immune system that boost protection against viruses: B cells that produce antibodies, and T cells that have multiple antiviral effects.
  • A new study confirms that people with MS on B cell therapies maintain a robust T cell response to COVID-19 vaccines, supporting the benefits of COVID-19 vaccination in this group, despite lower levels of antibodies.

There are two B cell depleting therapies currently approved for use in MS in Australia: Ocrevus (ocrelizumab) and Kesimpta (ofatumumab). Rituxan (rituximab) is another B cell depleting therapy sometimes used “off-label” in MS (that is, used for a purpose other than that specified by the Therapeutic Goods Administration (TGA), at the discretion of the treating clinician). These therapies reduce B cells in the immune system. It is thought that B cells drive much of the autoimmune disease attack on the brain and spinal cord in MS. However, B cells also have a beneficial effect as they produce protective antibodies against viruses, so it is important to understand whether people treated with these B cell depleting therapies can still mount a protective immune response against COVID-19. A new study published in the Multiple Sclerosis Journal has examined the antibody and T cell responses to SARS-CoV-2, the COVID-19 virus, in people on B cell depleting therapies for MS, after both vaccination and natural infection.

Vaccination boosts B and T cell immune responses

There are two major arms of the immune system that recognise specific invaders in the body. B cells of the immune system produce antibodies, large molecules that specifically bind foreign invaders (such as viruses and bacteria) in the body and then attract other immune cells to kill those invaders.  Vaccination boosts the level of specific antibodies that can be made against the target virus, such as COVID-19, so that there is an army of protection at the ready if we become infected with that particular virus.

However, vaccination can also activate another major arm of the immune system: the T cells. T cells also recognise specific foreign targets and have several anti-viral actions, including physically killing infected cells, boosting antiviral actions of other immune cells, and producing anti-viral molecules. A recent Australian study in healthy controls published in the prestigious journal, Nature Immunology, showed that the SARS-CoV-2 vaccine induces robust and long-lasting T cell responses to the virus that may contribute to long-term protection against COVID-19.

What was the aim of the study?

Several studies have shown that people on B cell depleting therapies for MS developed lower levels of protective antibodies in response to both SARS-CoV-2 vaccination, and to natural infection with the virus. However, other studies have shown that protection from infection, and from severe COVID-19 disease, may depend not only on antibodies, but on the T cell response to the virus. In this new study, researchers took a detailed looked at the antibody and T cell responses to SARS-CoV-2 over the first 17 months of the pandemic in a large group of people with MS on B cell depleting therapies (a total of 220 were on ocrelizumab; two were on rituximab).  The aim of the study was to help inform treatment decisions and management of SARS-CoV-2 vaccination for these people.

What did the researchers find?

The researchers confirmed the results of previous studies, that people on B cell depleting therapies produced a lower level of protective antibodies in response to SARS-CoV-2 vaccination, with only half (51%) showing evidence of antibodies, compared to healthy controls (100%), or to people with MS not on B cell depleting therapies (92%). They also found that the “protective quality” of the antibodies was reduced, that is, how strongly the antibodies can bind the virus and prevent infection. Interestingly, higher antibody responses to the person’s second SARS-CoV-2 vaccination were achieved when the vaccination was delayed for a longer time after B cell therapy, both in terms of levels and quality of the antibody response. In contrast, after either vaccination or natural infection, all people on B cell depleting therapies mounted a T cell response to the virus, to a level comparable to both other people with MS and healthy controls.

What does this mean for people with MS?

The results suggest that vaccination against the COVID-19 virus successfully boosts the immune response in people with MS on B cell depleting therapies. While the antibody quality and level of response to the vaccine is lower than in other people with MS and healthy controls, the second arm of the immune response, T cell response, is preserved. Delaying a COVID vaccination for a longer time after B cell depleting therapies for MS may result in a better antibody response to the vaccine.  People with MS on these B cell depleting therapies should discuss the timing of COVID vaccination and their treatment dosing with their health care team.

If you are on Ocrevus or Kesimpta treatment and test positive for COVID-19, please consult with your health care team as soon as possible, as early intervention with medications such as antivirals may be appropriate for a better outcome.  In the meantime, this research adds to our body of knowledge regarding both the B cell and T cell response after COVID-19 vaccination and natural infection, giving us confidence that the T cell response is working hard to provide some level of protection. This is why COVID-19 vaccinations are often still recommended in this population despite the known B cell depleting effects.

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Response to COVID vaccines in people with MS treated with B cell depleting therapies