Influenza Vaccination in Patients with Multiple Sclerosis on B Cell Depleting Therapies

Background: The use of B-cell depleting therapies (e.g. rituximab) in patients with multiple sclerosis, neuromyelitis optica, and other inflammatory disorders raises a clinical dilemma: given that the ability to generate an adequate protective antibody response is severely impaired due to B cell depletion, is it still beneficial to immunize patients, using the inactivated influenza vaccine?

Currently, the practice of vaccinating patients on B cell depleting therapies varies among neurologists. Many, assuming no benefit, choose not to vaccinate. However, antibody-mediated immune responses are not the only part of the immune system that help control influenza infection. T cell mediated immunity, although affected by the absence of B cells in many complex ways, is not abolished, and may offer protection, limit severity of the disease and reduce influenza-associated morbidity

Objectives: To provide a mechanistic rationale for immunizing against influenza in patients on B cell depleting therapies

Methods: Literature review and analysis

Results: Virus specific CD8+ T effector cells are important in clearing influenza infection. CD4+ T memory cells are critical in maintaining virus-specific CD8+ memory responses (Stambas et al). Influenza vaccine helps prime naïve T cells and generates virus specific T cells. Vaccinating also can boost pre-existent influenza specific memory T cells, which, unlike the specific antibodies, are effective against various strains of the virus. Dolphi et al showed that memory T cell CD8+ and CD4+ epitopes cross-react with internal viral protein sequences (matrix (M) and nucleoprotein (NP) that are highly conserved among various influenza strains and thus may offer protection even when the antibody response is either inadequate or directed against the wrong strain of the virus.

A study by Sridhar et al, conducted in the setting of 2009 H1N1 pandemic, highlighted the importance of cross-reactive cellular immunity by evaluating CD8+ T cell reponses prior to, during, and after the influenza infection and showed that those with pre-existent CD8+ T cells specific for highly conserved internal viral proteins experienced a less severe illness, despite the absence of neutralizing antibodies.

Wilkinson et al and McElhaney et al also showed that even in the setting of inadequate antibody responses, virus specific T cell mediated immunity against influenza virus offers protection and may reduce morbidity

Conclusions: Immunizing patients on B cell depleting therapies against influenza (using the inactivated virus vaccine) may be beneficial, as creating virus specific T cell immunity and boosting highly cross-reactive memory T cells from prior exposures to influenza are valuable in reducing the severity of the infection. Further studies are necessary to better understand the outcomes of multiple sclerosis patients vaccinated against influenza while on B cell depleting therapies, as compared to those who were not vaccinated