Systems vaccinology of the BNT162b2 mRNA vaccine in humans P ra bh u S. A ru na ch al am , M ad el ei ne K. D.

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including 3 rd dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is less after infection compared to all vaccines evaluated, but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks post-vaccination in some cases. SARS-CoV-2 antibody specificity, breadth and maturation are affected by imprinting from exposure history, and distinct histological and antigenic contexts in infection compared to vaccination.

Monocytes (Mo) and macrophages (Mϕ) are key components of the innate immune system and are involved in regulation of the initiation, development, and resolution of many inflammatory disorders. In addition, these cells also play important immunoregulatory and tissue-repairing roles to decrease immune reactions and promote tissue regeneration. Several lines of evidence have suggested a causal link between the presence or activation of these cells and the development of autoimmune diseases. In addition, Mo or Mϕ infiltration in diseased tissues is a hallmark of several autoimmune diseases. However, the detailed contributions of these cells, whether they actually initiate disease or perpetuate disease progression, and whether their phenotype and functional alteration are merely epiphenomena are still unclear in many autoimmune diseases. Additionally, little is known about their heterogeneous populations in different autoimmune diseases. Elucidating the relevance of Mo and Mϕ in autoimmune diseases and the associated mechanisms could lead to the identification of more effective therapeutic strategies in the future.

With the application and development of high-throughput sequencing technology in life and health sciences, massive multi-omics data brings the problem of efficient management and utilization. Database development and biocuration are the prerequisites for the reuse of these big data. Here, relying on China National GeneBank (CNGB), we present CNGB Sequence Archive (CNSA) for archiving omics data, including raw sequencing data and its further analyzed results which are organized into six objects, namely Project, Sample, Experiment, Run, Assembly and Variation at present. Moreover, CNSA has created a correlation model of living samples, sample information and analytical data on some projects. Both living samples and analytical data are directly correlated with the sample information. From either one, information or data of the other two can be obtained, so that all data can be traced throughout the life cycle from the living sample to the sample information to the analytical data. Complying with the data standards commonly used in the life sciences, CNSA is committed to building a comprehensive and curated data repository for storing, managing and sharing of omics data. We will continue to improve the data standards and provide free access to open-data resources for worldwide scientific communities to support academic research and the bio-industry. Database URL: https://db.cngb.org/cnsa/.

Various mechanical stresses can induce apoptosis of nucleus pulposus (NP) cells and intervertebral disc (IVD) degeneration in vivo, but the underlying molecular mechanism by which the number of NP cells is decreased in degenerated IVD is still not elucidated. The purpose of this study was to investigate whether the mitochondrial pathway is involved in compression-induced apoptosis of rabbit NP cells. The compression apparatus was used to investigate the effect of the compression in this process at one magnitude (1.0 MPa) for 6, 12, 18, 24 and 36 h. Cell viability was measured by cell counting kit-8. Apoptosis rate was analyzed by flow cytometry and the morphologic changes in apoptosis cells were observed by the phase-contrast microscopy and Hoechst 33258 staining. The apoptosis-related gene and protein synthesis, such as Bax, Bcl-2 and Caspase-3, was analyzed by real-time polymerase chain reaction and Western-blot, respectively. Mitochondrial function was evaluated by analyzing the mitochondrial permeability transition pore (MPTP), as well as reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). The results indicated that compression at the magnitude of all time points induced apoptosis of rabbit NP cells in a time-dependent manner, and the cell viability was reduced significantly. Furthermore, the compression at this level profoundly suppressed the functions of the mitochondria such as the opening of MPTP, the excessive production of ROS and the decreased MMP. Our findings suggest that the compression-induced IVD degeneration is mediated, at least in part, via the mitochondrial apoptotic pathway in NP cells.

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We studied 1859 subjects with confirmed COVID-19 from seven centers in Wuhan 1651 of whom recovered and 208 died. We interrogated diverse covariates for correlations with risk of death from COVID-19. In multi-variable Cox regression analyses increased hazards of in-hospital death were associated with several admission covariates: (1) older age (HR = 1.04; 95% Confidence Interval [CI], 1.03, 1.06 per year increase; P < 0.001); (2) smoking (HR = 1.84 [1.17, 2.92]; P = 0.009); (3) admission temperature per °C increase (HR = 1.32 [1.07, 1.64]; P = 0.009); (4) Log 10 neutrophil-to-lymphocyte ratio (NLR; HR = 3.30 [2.10, 5.19]; P < 0.001); (5) platelets per 10 E + 9/L decrease (HR = 0.996 [0.994, 0.998]; P = 0.001); ( 6) activated partial thromboplastin (aPTT) per second increase (HR = 1.04 [1.02, 1.05]; P < 0.001); (7) Log 10 D-dimer per mg/l increase (HR = 3.00 [2.17, 4.16]; P < 0.001); and (8) Log 10 serum creatinine per μmol/L increase (HR = 4.55 [2.72, 7.62]; P < 0.001). In piecewise linear regression analyses Log 10 NLR the interval from ≥0.4 to ≤1.0 was significantly associated with an increased risk of death. Our data identify covariates associated with risk of in hospital death in persons with COVID-19.

We studied admission and dynamic demographic, hematological and biochemical co-variates in 1449 hospitalized subjects with coronavirus infectious disease-2019 (COVID-19) in five hospitals in Wuhan, Hubei province, China. We identified two admission co-variates: age (Odds Ratio [OR] = 1.18, 95% Confidence Interval [CI] [1.02, 1.36]; P = 0.026) and baseline D-dimer (OR = 3.18 [1.48, 6.82]; P = 0.003) correlated with an increased risk of death in persons with COVID-19. We also found dynamic changes in four co-variates, Δ fibrinogen (OR = 6. 45 [1.31, 31.69]; P = 0.022), Δ platelets (OR = 0.95 [0.90-0.99]; P = 0.029), Δ C-reactive protein (CRP) (OR = 1.09 [1.01, 1.18]; P = 0.037), and Δ lactate dehydrogenase (LDH) (OR = 1.03 [1.01, 1.06]; P = 0.007) correlated with an increased risk of death. The potential risk factors of old age, high baseline D-dimer, and dynamic co-variates of fibrinogen, platelets, CRP, and LDH could help clinicians to identify and treat subjects with poor prognosis. data of hematological abnormalities in persons with . We studied hematological co-variates in 1449 hospitalized persons with COVID-19 in five hospitals in Wuhan, China, interrogating correlations of admission parameters with COVID-19 outcomes. Methods Study design and subjectsWe studied subjects in seven centers of five hospitals of