We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months joplink Hemoglobin Antibody. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.
Clinical and immunological features of chronic ulcerative stomatitis: a systematic review
Chronic ulcerative stomatitis (CUS) is a rare disease of the mucous membranes with characteristics similar to other autoimmune diseases. The aim of this study was to conduct a systematic review of the literature to recover all reported cases of CUS in order to summarize what are the clinical, demographic, microscopic, immunological features of CUS as well as, its therapeutic response to different drugs. A systematic review of the literature was carried out following the statements of preferred reporting items for systematic reviews and meta-analyzes (PRISMA).
The searches were performed in the electronic databases PubMed, Scopus, EMBASE, LILACS, Opengrey and Google scholar. Inclusion criteria was articles or abstracts reporting at least one case with a final diagnosis of CUS. A total of 696 records were identified through databases, and 25 studies were selected reporting 81 cases. CUS affects more females (92%), and a greater number of cases is reported in Caucasian patients (53%). The age of patients ranged from 20 to 86 years with a mean age of 60 years (±13.86), 15% of cases reported concomitantly skin lesions.
The clinical and histopathological characteristics of CUS are very similar to those of oral lichen planus. The direct immunofluorescence (DIF) remains the gold standard diagnostic resource and was performed in 69 cases, revealing a dotted pattern of deposition of stratified epithelium-specific antibodies (SES-ANA). The serum of 38 patients was collected for the performance of the indirect immunofluorescence (IIF) and the use of epithelial substrates such as monkey and guinea pig esophagus often resulted in positive SES-ANA IgG. Most patients were treated with antimalarials and the treatment of choice that proved to be effective is hydroxychloroquine (HCQ). This entity must be considered in the differential diagnosis of other autoimmune diseases, as it may be underreported.
Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases
Inflammatory diseases including COVID-19 are associated with a cytokine storm characterized by high interleukin-6 (IL-6) titers. In particular, while recent studies examined COVID-19 associated arrhythmic risks from cardiac injury and/or from pharmacotherapy such as the combination of azithromycin (AZM) and hydroxychloroquine (HCQ), the role of IL-6 per se in increasing the arrhythmic risk remains poorly understood.
The objective is to elucidate the electrophysiological basis of inflammation-associated arrhythmic risk in the presence of AZM and HCQ. IL-6, AZM and HCQ were concomitantly administered to guinea pigs in-vivo and in-vitro. Electrocardiograms, action potentials and ion-currents were analyzed. IL-6 alone or the combination AZM + HCQ induced mild to moderate reduction in heart rate, PR-interval and corrected QT (QTc) in-vivo and in-vitro. Notably, IL-6 alone was more potent than the combination of the two drugs in reducing heart rate, increasing PR-interval and QTc.
In addition, the in-vivo or in-vitro combination of IL-6 + AZM + HCQ caused severe bradycardia, conduction abnormalities, QTc prolongation and asystole. These electrocardiographic abnormalities were attenuated in-vivo by tocilizumab (TCZ), a monoclonal antibody against IL-6 receptor, and are due in part to the prolongation of action potential duration and selective inhibition of Na+, Ca2+ and K+ currents. Inflammation confers greater risk for arrhythmia than the drug combination therapy.
As such, in the setting of elevated IL-6 during inflammation caution must be taken when co-administering drugs known to predispose to fatal arrhythmias and TCZ could be an important player as a novel anti-arrhythmic agent. Thus, identifying inflammation as a critical culprit is essential for proper management.
Aggregation of high-frequency RBD mutations of SARS-CoV-2 with three VOCs did not cause significant antigenic drift
Variants of SARS-CoV-2 continue to emerge, posing great challenges in outbreak prevention and control. It is important to understand in advance the impact of possible variants of concern (VOCs) on infectivity and antigenicity. Here, we constructed one or more of the 15 high-frequency naturally occurring amino acid changes in the receptor-binding domain (RBD) of Alpha, Beta and Gamma variants. Single mutant of A520S, V367F, and S494P in above three VOCs enhanced infectivity in ACE2-overexpressing 293T cells of different species, LLC-MK2 and Vero cells. Aggregation of multiple RBD mutations significantly reduces the infectivity of the possible three VOCs. Regarding neutralization, it is noteworthy that E484K, N501Y, K417N, and N439K predispose to monoclonal antibodies (mAbs) protection failure in the 15 high-frequency mutations.
Most importantly, almost all possible VOCs (single RBD mutation or aggregation of multiple mutations) showed no more than a 4-fold decrease in neutralizing activity with convalescent sera, vaccine sera, and immune sera of guinea pigs with different immunogens, and no significant antigenic drift was formed. In conclusion, our pseudovirus results could reduce the concern that the aggregation of multiple high-frequency mutations in the RBD of the spike protein of the SARS-CoV-2 variants does not lead to severe antigenic drift, and this would provide value for vaccine development strategies. This article is protected by copyright.
Evaluation of the Re-emergence Risk of Human African Trypanosomiasis in the Southwestern Burkina Faso, A Gold-Bearing Mutation Area
Purpose: The boom in Burkina Faso’s artisanal gold mining since 2007 has attracted populations from Côte d’Ivoire and Guinea, which are the West African countries most affected by human African trypanosomiasis (HAT) and therefore increases its risk of re-emergence. Our aim was to update the HAT data in Burkina Faso in the risk of the re-emergence context with the advent of artisanal gold mining.
Methods: The study was carried out in southwestern Burkina Faso where entomological surveys were conducted using biconical traps in March 2017. Follow by an active medical survey in April 2017, which was targeted the gold panners in 7 villages closer to artisanal gold sites, using CATT, mini-anion exchange centrifugation technique, trypanolysis test (TL), and ELISA test to measure human/tsetse contacts. The buffy coat technique and the TL were also applied in pigs to check the reservoir role of human trypanosomes.
Results: Our results have shown no case of HAT among 958 individuals tested and all the 50 pigs were also negative, but the level of antibodies against tsetse saliva evidenced by ELISA revealed low human/tsetse contact. Moreover, gold panners practise agriculture and breeding in an infected tsetse area, which are increased the risk.
Conclusion: Our results illustrate that the risk of re-emergence is low. The passive surveillance system implemented in 2015 in southwestern Burkina Faso is needed to increase the sentinel sites to better cover this area by taking into account the gold mining. Finally, awareness-raising activities are needed among populations about HAT.
Hemoglobin Antibody |
|
| 1 mg | 644.4 EUR |
Hemoglobin Antibody |
|
| 1 mg | 644.4 EUR |
Hemoglobin antibody |
|
| 1 mg | 140 EUR |
Hemoglobin antibody |
|
| 1 mg | 109 EUR |
Hemoglobin antibody |
|
| 1 mg | 140 EUR |
Hemoglobin antibody |
|
| 1 mg | 325 EUR |
Hemoglobin antibody |
|
| 1 mg | 325 EUR |
Hemoglobin antibody |
|
| 500 ug | 425 EUR |
Hemoglobin antibody |
|
| 500 ug | 547.4 EUR |
Hemoglobin antibody |
|
| 1 mg | 186 EUR |