Interferon-β treatment reverses the detrimental effect of B cell depletion therapy on respiratory virus infection.

Abstract

Abstract There are several disease-modifying therapies (DMTs) used as treatments for multiple sclerosis. Depending on their mechanism, DMTs can increase morbidities of viral infections in patients, including SARS-CoV2 and influenza A virus (IAV). B cell depletion (BCD) with anti-CD20 antibodies and interferon-β (IFN-β) are two popular DMTs for MS. BCD increases the morbidity of acute viral infections in patients, whereas the antiviral properties of IFN-β are postulated to protect against infection. This study determined how BCD and IFN-β alone or in combination modulate IAV infection in mice. For BCD, we treated mice with 3 doses of anti-CD20 antibodies every 5 days beginning 7 days prior to IAV infection. For IFN-β, mice were treated on day 1 and 2 post infection. Mice treated only with BCD lost more weight compared to control mice. This increased morbidity was linked with higher levels of viral RNA and more neutrophils and inflammatory monocytes in the lungs at day 9 post-infection. T cell response to IAV was not altered by BCD. Mice treated only with IFN-β had no alteration in weight loss or myeloid cell infiltration in the lungs compared to controls. When adding IFN-β to BCD therapy, mice had significantly less weight loss and lower numbers of neutrophils and inflammatory monocytes in the lung compared to mice with BCD only. Addition of IFN-β to BCD did not improve IAV clearance. Our findings show that BCD increases virus-induced morbidity in mice, which reflects data from MS patients. Here we provide preclinical data showing that the addition of IFN-β can reverse the detrimental effect of BCD on viral infection. Therefore, the combination of non-interacting biologic therapies may mitigate morbidity during viral infection.