COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models

The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax—a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)—induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started

Low Speed Aerodynamic Analysis of the N2A Hybrid Wing–Body

Reduction of atmospheric emissions is currently a mandatory requirement for aircraft manufacturers. Several studies performed on Blended Wing–Body configurations showed a promising capability of reducing fuel consumption by increasing, at the same time, passengers’ transport capabilities. Although several aerodynamic studies are available at transonic speeds, low-speed evaluations of aerodynamic performances of Blended Wing Body aircrafts are less investigated. In this framework, the present paper deals with the aerodynamic performance of the N2A aircraft prototype at low-Mach number conditions. Aircraft longitudinal aerodynamics is addressed at M∞=0.2 with steady state three-dimensional RANS simulations carried out at two Reynolds numbers equal to 6.60×106 and 1.27×108, respectively. The former refers to an experimental test campaign performed at NASA Langley 14-by-22 foot subsonic tunnel, while the latter is related to free-flight conditions close to an approach and landing phase. Flowfield simulations are performed using the Computational Fluid Dynamic code FLUENT and the SU2 open-source code, currently adopted for research applications. Numerical solutions are validated by using available experimental data with reference to lift, drag, pitching moment and drag polar estimations. Pre-stall and post-stall aerodynamic behaviour through mean flow-field visualization along with the comparison of pressure distributions at several AoAs is addressed. Furthermore, the effect of convective discretization on a numerical solution for SU2 is discussed. Results indicate a good agreement with available experimental predictions. The present study aims to bridge existing computations at a Eulerian low-Mach number, with RANS computations and constitutes a further test-case for SU2 code with respect to a full aircraft configuration

Low Speed Aerodynamic Analysis of the N2A Hybrid Wing–Body

Reduction of atmospheric emissions is currently a mandatory requirement for aircraft manufacturers. Several studies performed on Blended Wing–Body configurations showed a promising capability of reducing fuel consumption by increasing, at the same time, passengers’ transport capabilities. Although several aerodynamic studies are available at transonic speeds, low-speed evaluations of aerodynamic performances of Blended Wing Body aircrafts are less investigated. In this framework, the present paper deals with the aerodynamic performance of the N2A aircraft prototype at low-Mach number conditions. Aircraft longitudinal aerodynamics is addressed at M∞=0.2 with steady state three-dimensional RANS simulations carried out at two Reynolds numbers equal to 6.60×106 and 1.27×108, respectively. The former refers to an experimental test campaign performed at NASA Langley 14-by-22 foot subsonic tunnel, while the latter is related to free-flight conditions close to an approach and landing phase. Flowfield simulations are performed using the Computational Fluid Dynamic code FLUENT and the SU2 open-source code, currently adopted for research applications. Numerical solutions are validated by using available experimental data with reference to lift, drag, pitching moment and drag polar estimations. Pre-stall and post-stall aerodynamic behaviour through mean flow-field visualization along with the comparison of pressure distributions at several AoAs is addressed. Furthermore, the effect of convective discretization on a numerical solution for SU2 is discussed. Results indicate a good agreement with available experimental predictions. The present study aims to bridge existing computations at a Eulerian low-Mach number, with RANS computations and constitutes a further test-case for SU2 code with respect to a full aircraft configuration

Adult normative values for the PATA Rate Test

During neurological evaluation, dysarthria is not rated using quantitative measures, but rather using a qualitative approach

DNA-Vaccine-Induced Immune Response Correlates with Lower Viral SARS-CoV-2 Titers in a Ferret Model

The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral circulation, with a significant number of deaths. To further explore alternative vaccination platforms, we developed COVID-eVax—a genetic vaccine based on plasmid DNA encoding the RBD domain of the SARS-CoV-2 spike protein. Here, we describe the correlation between immune responses and the evolution of viral infection in ferrets infected with the live virus. We demonstrate COVID-eVax immunogenicity as means of antibody response and, above all, a significant T-cell response, thus proving the critical role of T-cell immunity, in addition to the neutralizing antibody activity, in controlling viral spread

Epigenetic silencing of miR-145-5p contributes to brain metastasis

Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis