SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

Inflammation, as a feature of rheumatoid arthritis (RA), leads to the activation of endothelial cells (ECs). Activated ECs induce atherosclerosis through an increased expression of leukocyte adhesion molecules. Endothelial dysfunction (ED) is recognized as a failure of endothelial repair mechanisms. It is also an early preclinical marker of atherosclerosis and is commonly found in RA patients. RA is now established as an independent cardiovascular risk factor, while mechanistic determinants of ED in RA are still poorly understood. An expanding body of study has shown that EC at a site of RA is both active participant and regulator of inflammatory process. Over the last decade, a role for endothelial dysfunction in RA associated with cardiovascular disease (CVD) has been hypothesized. At the same time, several maintenance drugs targeting this phenomenon have been tested, which has promising results. Assessment of endothelial function may be a useful tool to identify and monitor RA patients.

Macrophages maintain a dynamic balance in physiology. Various known or unknown microenvironmental signals influence the polarization, activation and death of macrophages, which creates an imbalance that leads to disease. Rheumatoid arthritis (RA) is characterized by the massive infiltration of a variety of chronic inflammatory cells in synovia. Abundant activated macrophages found in RA synovia are an early hallmark of RA, and the number of these macrophages can be decreased after effective treatment. In RA, the proportion of M1 (pro‐inflammatory macrophages) is higher than that of M2 (anti‐inflammatory macrophages). The increased pro‐inflammatory ability of macrophages is related to their excessive activation and proliferation as well as an enhanced anti‐apoptosis ability. At present, there are no clinical therapies specific to macrophages in RA. Understanding the mechanisms and functional consequences of the heterogeneity of macrophages will aid in confirming their potential role in inflammation development. This review will outline RA‐related macrophage properties (focus on polarization, metabolism and apoptosis) as well as the origin of macrophages. The molecular mechanisms that drive macrophage properties also be elucidated to identify novel therapeutic targets for RA and other autoimmune disease.

BackgroundThe rate, prognostic impacts, and predisposing factors of major vascular complications (MVCs) in patients underwent venoarterial extracorporeal membrane oxygenation (VA-ECMO) by surgical cut-down are poorly understood. The purpose of this study was to identify these parameters in adult VA-ECMO patients.MethodsAdult postcardiotomy cardiogenic shock (PCS) patients receiving VA-ECMO by femoral surgical cut-down cannulation from January 2004 to December 2015 were enrolled in this study. Patients were separated into two groups depending on the presence of MVCs. Multivariate logistic regression was performed to identify factors independently associated with MVCs.ResultsOf 432 patients with PCS treated with VA-ECMO, 252 patients (58.3%) were weaned off VA-ECMO and 153 patients (35.4%) survived to discharge. MVCs were seen in 72 patients (16.7%), including bleeding or hematoma in the cannulation site (8.6%), limb ischemia requiring fasciotomy (8.6%), femoral artery embolism (0.7%), and retroperitoneal bleeding (0.7%). The rate of survival to discharge was 16.7 and 39.2% in patients with or without MVCs, respectively (p < 0.001). Obesity, concomitant with intra-aortic balloon pump (IABP), Sequential Organ Failure Assessment (SOFA) score at 24 h post-ECMO, and hemostasis disorder were shown to be associated with MVCs. MVCs were an independent risk factor for in-hospital mortality by multivariate analysis (odds ratio 3.91; 95% confidence interval, 1.67–9.14; p = 0.013).ConclusionsMVCs are common and associated with higher in-hospital mortality among adult PCS patients receiving peripheral VA-ECMO support. The obesity, concomitant with IABP, SOFA score at 24 h post-ECMO, and hemostasis disorder were independent risk factor of MVCs.

No abstract

IntroductionDifferential hypoxia is a pivotal problem in patients with femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) support. Despite recognition of differential hypoxia and attempts to deliver more oxygenated blood to the upper body, the mechanism of differential hypoxia as well as prevention strategies have not been well investigated.MethodsWe used a sheep model of acute respiratory failure that was supported with femoral VA ECMO from the inferior vena cava to the femoral artery (IVC-FA), ECMO from the superior vena cava to the FA (SVC-FA), ECMO from the IVC to the carotid artery (IVC-CA) and ECMO with an additional return cannula to the internal jugular vein based on the femoral VA ECMO (FA-IJV). Angiography and blood gas analyses were performed.ResultsWith IVC-FA, blood oxygen saturation (SO2) of the IVC (83.6 ± 0.8%) was higher than that of the SVC (40.3 ± 1.0%). Oxygen-rich blood was drained back to the ECMO circuit and poorly oxygenated blood in the SVC entered the right atrium (RA). SVC-FA achieved oxygen-rich blood return from the IVC to the RA without shifting the arterial cannulation. Subsequently, SO2 of the SVC and the pulmonary artery increased (70.4 ± 1.0% and 73.4 ± 1.1%, respectively). Compared with IVC-FA, a lesser difference in venous oxygen return and attenuated differential hypoxia were observed with IVC-CA and FA-IJV.ConclusionsDifferential venous oxygen return is a key factor in the etiology of differential hypoxia in VA ECMO. With knowledge of this mechanism, we can apply better cannula configurations in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0791-2) contains supplementary material, which is available to authorized users.

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.