Assembly of Immunogenic Protein Particles toward Advanced Synthetic Vaccines.

Immunogenic carrier proteins such as the non-toxic diphtheria toxin variant, cross-reacting material 197 (CRM197), are widely used in subunit vaccine formulations to boost immunogenicity of chemically conjugated antigens. Conjugate vaccines are inherently expensive due to laborious manufacturing steps. Here, this work develops a particulate vaccine platform based on using engineered Escherichia coli to assemble CRM197-antigen fusion proteins into discrete submicron-sized particles. This approach enables precise loading of diverse antigens and epitopes enhancing their immunogenicity. A cost-effective, high-yield, and scalable biomanufacturing process is developed. Purified particulate CRM197-antigen vaccines are ambient-temperature stable. CRM197 particles incorporating pathogen-specific antigens or epitopes from SARS-CoV-2, Streptococcus pyogenes (group A), and Mycobacterium tuberculosis induced cell-mediated and humoral immune responses mediating protective immunity in respective animal models of infection. The CRM197 particle vaccine platform is versatile, enabling co-delivery of selected antigens/epitopes together with immunogenic CRM197 as discrete stable particles avoiding laborious manufacture of soluble CRM197 and antigen followed by chemical conjugation.

Pharmacokinetics and safety of inhaled ivermectin in mice as a potential COVID-19 treatment.

Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic concentration of the drug in a clinically critical site of viral pathology. In this study, the pharmacokinetics (PK) and safety of inhaled dry powders of ivermectin with lactose were investigated in healthy mice. Female BALB/c mice received ivermectin formulation by intratracheal administration at high (3.15 mg/kg) or low doses (2.04 mg/kg). Plasma, bronchoalveolar lavage fluid (BALF), lung, kidney, liver, and spleen were collected at predetermined time points up to 48 h and analyzed for PK. Histological evaluation of lungs was used to examine the safety of the formulation. Inhalation delivery of ivermectin formulation showed improved pharmacokinetic performance as it avoided protein binding encountered in systemic delivery and maintained a high exposure above the in vitro antiviral concentration in the respiratory tract for at least 24 h. The local toxicity was mild with less than 20% of the lung showing histological damage at 24 h, which resolved to 10% by 48 h.

Pyrolysis of waste surgical masks into liquid fuel and its life-cycle assessment.

Pyrolysis of the middle layer of a surgical mask (MLM) and inner and outer layers of a surgical mask (IOM) was performed to assess their potential valorization as waste-to-energy feedstocks, and the characteristics of the resulting products were investigated. Pyrolysis of the main organics in waste surgical masks occurred at a very narrow temperature range of 456-466 °C. The main product was carbon-rich and oxygen-deficient liquid oil with a high heating value (HHV) of 43.5 MJ/kg. From the life-cycle perspective, environmental benefits and advantages of this upcycling approach were verified compared with conventional waste management approaches. This study advocated the potential application of waste surgical masks as feedstocks for fuels and energy, which is beneficial to mitigate plastic pollution and achieve sustainable plastic waste-to-energy upcycling, simultaneously.

A machine learning framework to quantify and assess the impact of COVID-19 on the power sector: An Indian context

As the COVID-19 continues to disrupt the global norms, there is the requirement of modelling frameworks to accurately assess and quantify the impact of the pandemic on the electricity sector and its emissions. In this study, we devise machine learning models to estimate the pandemic induced reduction in electricity consumption based on weather, econometrics, and social-distancing parameters for seven major Indian states. As per our baseline electricity consumption model, we find that the electricity consumption dropped by 15-33% in 2020 (March-May) during the complete lockdown phase, followed by 6-13% (June-August) during the unlock phases and gradually reached the norms by September 2020. As a result, the net CO2 emissions from power generation in 2020 dropped by 7% and 5% compared to 2018 and 2019 respectively. Amidst the ongoing second wave since mid-April 2021, we projected the electricity consumption across states from May-August by accounting for two scenarios. Under the reference and worst-case scenarios, the electricity consumption approximates 106% and 96% of the non-pandemic situation, respectively. The modelling framework developed in this study is purely data-oriented, cross-deployable across spatio-temporal scales and can serve as a valuable tool to inform current and future energy policies amidst and post COVID-19.

The Effect of the COVID-19 Vaccine on Daily Cases and Deaths Based on Global Vaccine Data.

BACKGROUND: Coronavirus disease 2019 (COVID-19), a global pandemic, has caused over 216 million cases and 4.50 million deaths as of 30 August 2021. Vaccines can be regarded as one of the most powerful weapons to eliminate the pandemic, but the impact of vaccines on daily COVID-19 cases and deaths by country is unclear. This study aimed to investigate the correlation between vaccines and daily newly confirmed cases and deaths of COVID-19 in each country worldwide. METHODS: Daily data on firstly vaccinated people, fully vaccinated people, new cases and new deaths of COVID-19 were collected from 187 countries. First, we used a generalized additive model (GAM) to analyze the association between daily vaccinated people and daily new cases and deaths of COVID-19. Second, a random effects meta-analysis was conducted to calculate the global pooled results. RESULTS: In total, 187 countries and regions were included in the study. During the study period, 1,011,918,763 doses of vaccine were administered, 540,623,907 people received at least one dose of vaccine, and 230,501,824 people received two doses. For the relationship between vaccination and daily increasing cases of COVID-19, the results showed that daily increasing cases of COVID-19 would be reduced by 24.43% [95% CI: 18.89, 29.59] and 7.50% [95% CI: 6.18, 8.80] with 10,000 fully vaccinated people per day and at least one dose of vaccine, respectively. Daily increasing deaths of COVID-19 would be reduced by 13.32% [95% CI: 3.81, 21.89] and 2.02% [95% CI: 0.18, 4.16] with 10,000 fully vaccinated people per day and at least one dose of vaccine, respectively. CONCLUSIONS: These findings showed that vaccination can effectively reduce the new cases and deaths of COVID-19, but vaccines are not distributed fairly worldwide. There is an urgent need to accelerate the speed of vaccination and promote its fair distribution across countries.

Association between temperature and COVID-19 transmission in 153 countries.

The WHO characterized coronavirus disease 2019 (COVID-19) as a global pandemic. The influence of temperature on COVID-19 remains unclear. The objective of this study was to investigate the correlation between temperature and daily newly confirmed COVID-19 cases by different climate regions and temperature levels worldwide. Daily data on average temperature (AT), maximum temperature (MAXT), minimum temperature (MINT), and new COVID-19 cases were collected from 153 countries and 31 provinces of mainland China. We used the spline function method to preliminarily explore the relationship between R0 and temperature. The generalized additive model (GAM) was used to analyze the association between temperature and daily new cases of COVID-19, and a random effects meta-analysis was conducted to calculate the pooled results in different regions in the second stage. Our findings revealed that temperature was positively related to daily new cases at low temperature but negatively related to daily new cases at high temperature. When the temperature was below the smoothing plot peak, in the temperate zone or at a low temperature level (e.g., <25th percentiles), the RRs were 1.09 (95% CI: 1.04, 1.15), 1.10 (95% CI: 1.05, 1.15), and 1.14 (95% CI: 1.06, 1.23) associated with a 1°C increase in AT, respectively. Whereas temperature was above the smoothing plot peak, in a tropical zone or at a high temperature level (e.g., >75th percentiles), the RRs were 0.79 (95% CI: 0.68, 0.93), 0.60 (95% CI: 0.43, 0.83), and 0.48 (95% CI: 0.28, 0.81) associated with a 1°C increase in AT, respectively. The results were confirmed to be similar regarding MINT, MAXT, and sensitivity analysis. These findings provide preliminary evidence for the prevention and control of COVID-19 in different regions and temperature levels.

The COVID-19 pandemic necessitates a shift to a plastic circular economy.

The COVID-19 pandemic is exacerbating plastic pollution. A shift in waste management practices is thus urgently needed to close the plastic loop, requiring governments, researchers and industries working towards intelligent design and sustainable upcycling.

The spatial clustering analysis of COVID-19 and its associated factors in mainland China at the prefecture level

Coronavirus disease 2019 (COVID-19) has become a worldwide public health threat. Many associated factors including population movement, meteorological parameters, air quality and socioeconomic conditions can affect COVID-19 transmission. However, no study has combined these various factors in a comprehensive analysis. We collected data on COVID-19 cases and the factors of interest in 340 prefectures of mainland China from 1 December 2019 to 30 April 2020. Moran's I statistic, Getis-Ord Gi⁎ statistic and Kulldorff's space-time scan statistics were used to identify spatial clusters of COVID-19, and the geographically weighted regression (GWR) model was applied to investigate the effects of the associated factors on COVID-19 incidence. A total of 67,449 laboratory-confirmed cases were reported during the study period. Wuhan city as well as its surrounding areas were the cluster areas, and January 25 to February 21, 2020, was the clustering time of COVID-19. The population outflow from Wuhan played a significant role in COVID-19 transmission, with the local coefficients varying from 14.87 to 15.02 in the 340 prefectures. Among the meteorological parameters, relative humidity and precipitation were positively associated with COVID-19 incidence, while the average wind speed showed a negative correlation, but the relationship of average temperature with COVID-19 incidence inconsistent between northern and southern China. NO2 was positively associated, and O3 was negatively associated, with COVID-19 incidence. Environment with high levels of inbound migration or travel, poor ventilation, high humidity or heavy rainfall, low temperature, and high air pollution may be favorable for the growth, reproduction and spread of SARS-CoV-2. Therefore, applying appropriate lockdown measures and travel restrictions, strengthening the ventilation of living and working environments, controlling air pollution and making sufficient preparations for a possible second wave in the relatively cold autumn and winter months may be helpful for the control and prevention of COVID-19.

A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2.

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of the MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion-exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor-binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.