ABSTRACT
To control the ongoing COVID-19 pandemic, CoronaVac (Sinovac), an inactivated vaccine, has been granted emergency use authorization by many countries. However, the underlying mechanisms of the inactivated COVID-19 vaccine-induced immune response remain unclear, and little is known about its features compared to SARS-CoV-2 infection. Here, we implemented single-cell RNA sequencing (scRNA-seq) to profile longitudinally collected PBMCs (peripheral blood mononuclear cells) in six individuals immunized with CoronaVac and compared these to the profiles of COVID-19 infected patients from a Single Cell Consortium. Both inactivated vaccines and SARS-CoV-2 infection drove changes in immune cell type proportions, caused B cell activation and differentiation, and induced the expression of genes associated with antibody production in the plasma. The inactivated vaccine and SARS-COV-2 infection also caused alterations in peripheral immune activity such as interferon response, inflammatory cytokine expression, innate immune cell apoptosis and migration, effector T cell exhaustion and cytotoxicity, however, the magnitude of change was greater in COVID-19 patients, especially those with severe disease, than in immunized individuals. Further analyses revealed a distinct peripheral immune cell phenotype associated with CoronaVac immunization (HLA class II upregulation and IL21R upregulation in naive B cells) versus SARS-CoV-2 infection (HLA class II downregulation and IL21R downregulation in naive B cells severe disease). There were also differences in the expression of important genes associated with proinflammatory cytokines and thrombosis. In conclusion, this study provides a single-cell atlas of the systemic immune response to CoronaVac immunization and reveals distinct immune responses between inactivated vaccines and SARS-CoV-2 infection.
ABSTRACT
Objective:To investigate the effects of caspase-11 non-canonical inflammasome on the Leptospira interrogans ( L. interrogans)-induced secretion of inflammatory cytokines in J774A.1 cells. Methods:Murine mononuclear macrophage cells (J774A.1) were infected with L. interrogans strain 56601. Expression of caspase-11, IL-1β, IL-1α and IL-18 at mRNA level in J774A.1 cells were detected by real-time RT-PCR. The levels of caspase-11, IL-1β, IL-1α and IL-18 in the culture supernatants of J774A.1 cells were detected by ELISA. Results:Real-time RT-PCR showed that caspase-11 expression at mRNA level was 5.12, 14.21, 8.94, 14.06, 18.58 and 0.93 times of that in uninfected cells after 1, 2, 4, 8, 12 and 24 h of L. interrogans infection, and respectively decreased to 0.10, 0.07, 0.10, 0.09, 0.07 and 0.45 times after caspase-11 inhibitor intervention ( P<0.05). Expression of IL-1β, IL-1α and IL-18 at mRNA level was significantly increased after infection ( P<0.05). After the intervention with caspase-11 inhibitor, IL-1β mRNA decreased to 0.05, 0.03, 0.02, 0.05, 0.06 and 0.02 times ( P<0.05); IL-1α mRNA decreased to 0.14, 0.07, 0.15, 0.10, 0.03 and 0.06 times ( P<0.05); IL-18 mRNA decreased to 0.08, 0.10, 0.16, 0.18, 0.10 and 0.07 times ( P<0.05). ELISA results showed that the expression of caspase-11, IL-1β, IL-1α and IL-18 at protein level was significantly increased. After the intervention with caspase-11 inhibitor, caspase-11 level decreased to 43.07, 41.64, 51.96, 86.56, 105.36, and 129.95 pg/ml ( P<0.05); IL-1β level decreased to 15.01, 14.19, 68.02, 31.20, 173.13 and 104.98 pg/ml ( P<0.05); IL-1α level decreased to 12.14, 15.40, 38.01, 21.97, 24.48 and 27.09 pg/ml ( P<0.05); IL-18 level decreased to 96.27, 102.21, 85.34, 116.28, 155.36 and 114.03 pg/ml ( P<0.05). Conclusions:Caspase-11 non-canonical inflammasome was involved in the mediation of IL-1β, IL-1α and IL-18 secretion in mouse mononuclear macrophages after L. interrogans infection.