Responses to Vaccination in Patients Taking Immunotherapies

October 2022

Many disease-modifying immunotherapies for neuroimmunologic diseases are now available. Vaccination is crucial to reduce the risk of infection in these patients, but immunotherapies may impair vaccine responses.

A comprehensive review of vaccine responses in patients taking immunotherapies for neuroimmunologic diseases summarizes the current knowledge and recommendations for appropriate timing between vaccination and therapy to maximize vaccine effectiveness. The review concentrated on studies for vaccine responses in patients taking disease-modifying therapies for multiple sclerosis or neuromyelitis optica spectrum disorder because therapies for these disorders are also used to treat other diseases.

The authors found that the inhibition of immune response to vaccines typically depends on the overall mode of action of the immunotherapy. However, even therapies with similar modes of action may have different effects on immune responses to vaccination. For example, fingolimod and natalizumab both impair immune cell migration but have different effects on vaccine responses, possibly because of their different molecular mechanisms of action. Fingolimod, a modulator of the sphingosine 1 phosphate receptor, seems to decrease the humoral immune response to vaccination. In contrast, 2 studies have found that patients taking natalizumab, a monoclonal antibody that binds to an integrin, were able to mount sufficient responses to vaccines.

Even when vaccine responses are reduced, the responses may be adequate for protection. For example, studies showed that patients taking ocrelizumab, a B-cell–depletion therapy, had lower humoral responses to vaccines. However, patients who did respond were still seroprotected, and the authors suggested that patients should still receive seasonal flu vaccines even during treatment.

In addition to natalizumab, studies have shown good immune responses to vaccination in patients taking teriflunomide, interferons, dimethyl fumarate, or tocilizumab.

Clinicians can find specific guidelines and recommendations for vaccinating patients who have neuroimmunologic diseases from professional societies and regulatory agencies. These groups recommend screening for infections before starting immunotherapies. With few exceptions, live vaccines should not be used in patients while they are taking immunotherapy, but inactivated vaccines are safe.

The authors stressed the importance of timing between vaccination and the initiation of immunotherapy. Timing should depend on the half-life of the immunotherapy. The review includes a table listing dozens of immunotherapeutic agents and suggested time intervals between vaccination and the initiation of treatment or between treatment with an immunotherapy and vaccination with a live vaccine. For example, a delay of 2 to 4 weeks is recommended between vaccination with an inactivated vaccine and initiation of dimethyl fumarate, and a delay of >6 weeks is recommended between vaccination and ocrelizumab therapy.

The disease status should also be considered. The authors stated, “vaccinations must be avoided during relapses or exacerbations of neuroimmunological diseases.”

The results of studies of the effects of immunotherapy on humoral and immune cell response to SARS-CoV-2 vaccination have generally mirrored those for other vaccines. Reassuringly, some studies have shown that T-cell responses are preserved even in patients taking anti-CD20 therapies that decrease the humoral response to SARS-CoV-2 vaccination. Although the authors recommended consideration of time intervals between therapy and vaccination, “given the risk of infection during the pandemic, the relative timing of vaccination in relation to dosing of immunotherapy is of minor relevance even if the immune response is reduced.”

The authors concluded that despite the reduced immune responses caused by many immunotherapies, vaccination is still an important tool to prevent infection and poor outcomes in patients with neuroimmunologic disease.


Winkelmann A, Loebermann M, Barnett M, et al. Vaccination and immunotherapies in neuroimmunological diseases. Nat Rev Neurol. 2022;18(5):289-306.

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