One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 10⁶ pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.     

Exploring Challenges of Health System in Iranian Traditional Medicine: A Qualitative Study

BackgroundTraditional medicine is a complete system, including diagnostic methods, etiology and treatment based on interpersonal differences.Owing to a lack of investigations in the field of Iranian traditional medicine as well as its many present challenges, certain studies in this area can prove quite practical in identifying and solving ongoing challenges. This study investigates the challenges of the health system in Iranian traditional medicine in the context of control levers.MethodsThe study was qualitative content analysis. A framework analysis, “Control Knob Approach”, was considered appropriate to promote apprehension of challenges of health systems in Iranian traditional medicine. Data were collected by purposeful sampling through in-depth and semi-structured individual interviews with 35 experts of Iranian traditional medicine. Directed content analysis was used to analyze the data, which extracted the initial codes after performing the recorded interviews on paper and immersing them in the data analysis.ResultsUpon analysis of data by Iranian medicine experts, five main categories including financing, payment system, regulations, behavior and organization were defined alongside 13 subcategories.ConclusionAccording to current challenges and the tendency of society to receive traditional medicine services, as well as the long history of traditional medicine in Iran, fair access to traditional medicine services should be provided. This access must be through the production of indigenous knowledge and the formulation of regulatory and educational policies and guidelines and the empowerment of relevant, healthy, effective, evidence-based and cost-effective forces.     

我国血吸虫病消除阶段健康教育与健康促进面临的挑战及对策

健康教育与健康促进是我国血吸虫病综合防控的重要措施之一，可提高流行区居民参与血防工作的依从性，有效避免或减少人群血吸虫感染。近年来，我国血吸虫病综合防控成效显著，已实现了传播控制目标，正向传播阻断乃至消除目标迈进。本文就健康教育与健康促进在我国血吸虫病防控中的作用及当前面临的挑战进行了分析，并就如何在消除阶段推进血吸虫病健康教育与健康促进工作提出针对性建议。     

Efficacy of a high potency O1 Manisa foot-and-mouth disease vaccine in cattle against heterologous challenge with a field virus from the O/ME-SA/Ind-2001 lineage collected in North Africa

Outbreaks of foot-and-mouth disease (FMD) in North Africa (2013) and the Gulf States (2013) of the Middle East have been caused by a FMD viral lineage (O/ME-SA/Ind-2001) that was before 2013 restricted to the Indian Sub-continent. This study was undertaken to assess the in vivo efficacy of a FMD virus emergency vaccine type O₁ Manisa against heterologous challenge with a representative field virus (O/ALG/3/2014) from this emerging lineage. This widely available vaccine was selected since in vitro vaccine-matching results gave inconclusive results as to whether or not it would be protective. Three groups of five cattle were vaccinated with O₁ Manisa (homologous potency ≥6PD₅₀/dose) using study guidelines outlined in the European Pharmacopeia, and challenged at 21 days post-vaccination by tongue inoculation. All animals that were vaccinated with the lowest dose (1/16) of vaccine developed generalised FMD, defined as vesicular lesions at the feet. One animal vaccinated with a 1/4 dose of the vaccine also developed generalised disease, as did two animals vaccinated with the full dose of vaccine. These results indicate that the heterologous potency of this high potency O₁ Manisa vaccine was approximately 3.5 PD₅₀/dose. These data support the use of the O₁ Manisa vaccine for FMD control in areas where FMDV is endemic e.g. North Africa, and motivate further studies to evaluate other vaccine candidates (or multivalent combinations) that might be potentially used for emergency purposes in FMD-free settings.     

Multiple Selectin Blockade With a Small-Molecule Selectin Inhibitor Does Not Affect Survival After a Second Inflammatory Challenge With Nonlethal LPS

The effects of anti-adhesion molecule antibodies on the blockade of leukocyte-endothelial interactions have the potential of decreasing survival through possibly increased infection vulnerability. The aim of this study was to determine the effect of a small-molecule selectin inhibitor (TBC-1269) on both liver response and survival to a nonlethal lipopolysaccharide (LPS) challenge after hemorrhagic shock. Ninety-six Sprague-Dawley rats were subjected to a model of uncontrolled hemorrhagic shock. Six groups of animals were included in this study ( n = 16 per group): sham/saline, sham/LPS, shock/saline, shock/LPS, shock/TBC1269, and shock/TBC-1269/LPS. Experimental design consisted of the development of hemorrhagick shock (3 mL/100 g) in a 15-min period, tail amputation and drug administration at 30 min, and subsequent resuscitation to maintain mean arterial pressure at 70mm Hg. A septic challenge was produced with 0.1 mg/kg of LPS ( Escherichia coli type 78H4086; Sigma Chemical, St. Louis, MO) given intravenously via penile vein at 20 h. Liver injury tests (alanine aminotransferase, ALT), liver myeloperoxidase, liver histology, and 21-day survival were evaluated. Statistical analysis included the Bartlett test for equality of variance, a two-way analysis of variance (ANOVA), and overall followed by pairwise log-rank test for survival. Significant improvements in liver function and histology were observed in animals treated with TBC-1269 with or without a nonlethal septic challenge. Neutrophil infiltration, as evidenced by liver myeloperoxidase (MPO) was significantly decreased in animals treated with TBC-1269 alone and those having LPS administration after TBC-1269 treatment. We conclude that TBC-1269, multisectin blocker, was effective in reducing liver damage even with the addition of a second inflammatory insult as the nonlethal LPS challenge used in this study.