Source: https://www.science.org/doi/10.1126/scitranslmed.adh4529
Editor’s summary
Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primary thought to be mediated by B cells and antibodies. However, T cell responses are also activated by SARS-CoV-2 infection and vaccination and may be especially important in protecting individuals who lack B cells. Here, Zonozi et al. characterized the T cell response to SARS-CoV-2 vaccination and infection in individuals lacking B cells due to treatment with rituximab or due to a primary immunodeficiency. Not only were virus-specific CD4+ and CD8+ T cells elicited by both infection and vaccination, but the T cells exhibited greater reactivity and proliferative capacity as compared with controls. Furthermore, the authors evaluated clinical outcomes of SARS-CoV-2 infection in B cell–deficient individuals, observing that vaccination still reduced the risk of severe disease. Together, these results demonstrate a protective role for SARS-CoV-2–specific T cells and highlight the importance of SARS-CoV-2 vaccination in B cell–deficient patient populations. —Courtney Malo
Abstract
Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease and mortality from coronavirus disease 2019 (COVID-19), but the immune responses and clinical outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have yet to be fully defined. Here, we evaluate the cellular immune responses after both SARS-CoV-2 infection and vaccination in patients receiving the anti-CD20 therapy rituximab (RTX) and those with low B cell counts due to common variable immune deficiency (CVID) disease. Assessment of effector and memory CD4+ and CD8+ T cell responses to SARS-CoV-2 revealed elevated reactivity and proliferative capacity after both infection and vaccination in B cell–deficient individuals, particularly within the CD8+ T cell compartment, in comparison with healthy controls. Evaluation of clinical outcomes demonstrates that vaccination of RTX-treated individuals was associated with about 4.8-fold reduced odds of moderate or severe COVID-19 in the absence of vaccine-induced antibodies. Analysis of T cell differentiation demonstrates that RTX administration increases the relative frequency of naïve CD8+ T cells, potentially by depletion of CD8+CD20dim T cells, which are primarily of an effector memory or terminal effector memory (TEMRA) phenotype. However, this also leads to a reduction in preexisting antiviral T cell immunity. Collectively, these data indicate that individuals with B cell deficiencies have enhanced T cell immunity after both SARS-CoV-2 infection and vaccination that potentially accounts for reduced hospitalization and severe disease from subsequent SARS-CoV-2 infection.
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