A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing ...the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 46%), fatigue (47 44%), headache (42 39%), and muscle pain (18 17%. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
Abstract
The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic ...resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.
Covalent organic frameworks (COFs) have emerged as an exciting new class of porous materials constructed by organic building blocks via dynamic covalent bonds. They have been extensively explored as ...potentially superior candidates for electrode materials, electrolytes, and separators, due to their tunable chemistry, tailorable structures, and well‐defined pores. These features enable rational design of targeted functionalities, facilitate the penetration of electrolytes, and enhance ion transport. This review provides an in‐depth summary of the recent progress in the development of COFs for diverse battery applications, including lithium‐ion, lithium–sulfur, sodium‐ion, potassium‐ion, lithium–CO2, zinc‐ion, zinc–air batteries, etc. This comprehensive synopsis pays particular attention to the structure and chemistry of COFs and novel strategies that have been implemented to improve battery performance. Additionally, current challenges, possible solutions, and potential future research directions on COFs for batteries are discussed, laying the groundwork for future advances for this exciting class of material.
Covalent organic frameworks (COFs) are promising candidates in energy storage applications. This review summarizes the recent progress of COFs for batteries, including lithium‐ion, lithium–sulfur, sodium/potassium‐ion, lithium–CO2, and zinc‐ion/–air batteries. This review mainly focuses on the structure and chemistry of COFs and novel strategies implemented to improve battery performance along with current challenges, possible solutions, and potential future research directions.
This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an ...appropriate dose of the candidate vaccine for an efficacy study.
This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.
603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.
The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.
National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
The development of versatile nanotheranostic platforms that integrate both diagnostic and therapeutic functions have always been an intractable challenge in precise cancer treatment. Herein, an ...aptamer‐tethered deoxyribonucleic acids‐gold particle (Apt‐DNA‐Au) nanomachine has been developed for in situ imaging and targeted multimodal synergistic therapy of mammary carcinoma. Upon specifically internalized into MCF‐7 cells, the tumor‐related TK1 mRNA activates the Apt‐DNA‐Au nanomachine by DNA strand displacement cascades, resulting in the release of the fluorophore and antisense DNA as well as the aggregation of AuNPs for in situ imaging, suppression of survivin expression and photothermal therapy, respectively. Meanwhile, the controlled released drugs are used for chemotherapy, while under the laser irradiation the loaded photosensitizer produces reactive oxygen species (ROS) for photodynamic therapy. The results confirm that the proposed Apt‐DNA‐Au nanomachine provides a powerful nanotheranostic platform for in situ imaging‐guided combinatorial anticancer therapy.
A multifunctional DNA‐Au nanomachine which can be triggered by endogenous tumor growth‐related TK1 mRNA has been devised as the combinatorial theranostic agent for fluorescence imaging‐guided chemo, genic, photodynamic, and photothermal synergistic targeted therapy of breast cancer. This theranostic nanoplatform achieves the significant inhibition of tumor growth and improvement of therapeutic efficacy through in situ imaging.
Nanocarrier surface chemistry plays a vital role in mediating cell internalization and enhancing delivery efficiency during in vivo chemotherapy. Inspired by the ability of proteins to alter their ...conformation to mediate functions, a pH‐/thermal‐/glutathione‐responsive polymer zipper consisting of cell‐penetrating poly(disulfide)s and thermosensitive polymers bearing guanidinium/phosphate (Gu+/pY−) motifs to spatiotemporally tune the surface composition of nanocarriers for precise tumor targeting and efficient drug delivery is developed. Surface engineering allows the nanocarriers to remain undetected during blood circulation and favors passive accumulation at tumor sites, where the acidic microenvironment and photothermal heating break the pY−/Gu+ binding and rupture the zipper, thereby exposing the penetrating shell and causing enhanced cellular uptake via counterion‐/thiol‐/receptor‐mediated endocytosis. The in vivo study demonstrates that by manipulating the surface states on command, the nanocarriers show longer blood circulation time, minimized uptake and drug leakage in normal organs, and enhanced accumulation and efficient drug release at tumor sites, greatly inhibiting tumor growth with only slight damage to normal tissues. If integrated with a photothermal dye approved by the U.S. Food and Drug Administration (FDA), polymer zipper would provide a versatile protocol for engineering nanomedicines with high selectivity and efficiency for clinical cancer treatment.
pH‐/thermal‐/glutathione‐responsive polymer zippers are screened and explored to tune nanocarrier surface compositions on command for precise tumor targeting in vivo. The nanocarriers remain stealthy during blood circulation, but their surfaces are activated by the acidic microenvironment and photothermal heating at tumor sites for enhanced cellular uptake and efficient drug release, presenting a versatile engineering strategy for nanomedicinal use.
In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating ...HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
The rapid increase in both the quantity and complexity of data that are being generated daily in the field of environmental science and engineering (ESE) demands accompanied advancement in data ...analytics. Advanced data analysis approaches, such as machine learning (ML), have become indispensable tools for revealing hidden patterns or deducing correlations for which conventional analytical methods face limitations or challenges. However, ML concepts and practices have not been widely utilized by researchers in ESE. This feature explores the potential of ML to revolutionize data analysis and modeling in the ESE field, and covers the essential knowledge needed for such applications. First, we use five examples to illustrate how ML addresses complex ESE problems. We then summarize four major types of applications of ML in ESE: making predictions; extracting feature importance; detecting anomalies; and discovering new materials or chemicals. Next, we introduce the essential knowledge required and current shortcomings in ML applications in ESE, with a focus on three important but often overlooked components when applying ML: correct model development, proper model interpretation, and sound applicability analysis. Finally, we discuss challenges and future opportunities in the application of ML tools in ESE to highlight the potential of ML in this field.
Lead halide perovskite quantum dots (QDs) are promising electrochemiluminescence (ECL) nanoemitters due to their fascinating photophysical properties. However, due to their poor structural stability ...against the external environment, the trade‐off between their colloidal stability and carrier injection/transport efficiency is a major challenge in the advancement of perovskite‐based ECL technology. In this work, intense and stable ECL from CsPbBr3 (CPB) QDs is achieved by simultaneously encapsulating CPB QDs and coreactant (CoR) into in situ generated SiO2 matrix via hydrolysis of tetramethyl orthosilicate. The well‐designed architecture of the as‐obtained CPB‐CoR@SiO2 nanocomposites (NCs) guarantees not only greatly improved stability thanks to the peripheral SiO2 protecting matrix, but also efficient self‐enhanced ECL between CPB and the intra‐coreactants. Consequently, by elaborately selecting the CoR molecules with different tertiary/secondary amines and functional groups, multifold higher (up to 10.2 times) ECL efficiencies are obtained for the CPB‐CoR@SiO2 NCs alone in reference to the standard Ru(bpy)32+/tri‐n‐propylamine system. This work provides an efficient design strategy for obtaining stable and highly efficient ECL from perovskite QDs, and offers a new perspective for the development and application of perovskite‐based ECL system.
Ternary CsPbBr3 perovskite suprastructures with self‐enhanced electrochemiluminescence and improved stability is prepared by simultaneously encapsulating CsPbBr3 quantum dots and coreactant into in situ generated SiO2 matrix via hydrolysis of tetramethyl orthosilicate. The obtained nanocomposites exhibit higher (up to 10.2 times) electrochemiluminescence efficiencies in reference to the standard Ru(bpy)32+/tri‐n‐propylamine system.
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