Publications by authors named "Miao Xu"

427 Publications

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

Emerg Microbes Infect 2021 Jul 18:1-28. Epub 2021 Jul 18.

National Institutes for Food and Drug Control, No.31, Huatuo Road, Daxing District, Beijing 102629, People's Republic of China.

Since the outbreak of COVID-19, a variety of vaccine platforms have been developed. Amongst these, inactivated vaccines have been authorized for emergency use or conditional marketing in many countries. To further enhance the protective immune responses in populations that have completed vaccination regimen, we investigated the immunogenic characteristics of different vaccine platforms and tried homologous or heterologous boost strategy post two doses of inactivated vaccines in a mouse model. Our results showed that the humoral and cellular immune responses induced by different vaccines when administered individually differ significantly. In particular, inactivated vaccines showed relatively lower level of neutralizing antibody and T cell responses, but a higher IgG2a/IgG1 ratio compared with other vaccines. Boosting with either recombinant subunit, adenovirus vectored or mRNA vaccine after two-doses of inactivated vaccine further improved both neutralizing antibody and Spike-specific Th1-type T cell responses compared to boosting with a third dose of inactivated vaccine. Our results provide new ideas for prophylactic inoculation strategy of SARS-CoV-2 vaccines.
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http://dx.doi.org/10.1080/22221751.2021.1957401DOI Listing
July 2021

Formulation Strategies for Bacteriophages to Target Intracellular Bacterial Pathogens.

Adv Drug Deliv Rev 2021 Jul 13:113864. Epub 2021 Jul 13.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address:

Bacteriophages (Phages) are antibacterial viruses that are unaffected by antibiotic drug resistance. Many Phase I and Phase II phage therapy clinical trials have shown acceptable safety profiles. However, none of the completed trials could yield data supporting the promising observations noted in the experimental phage therapy. These trials have mainly focused on phage suspensions without enough attention paid to the stability of phage during processing, storage, and administration. This is important because in vivo studies have shown that the effectiveness of phage therapy greatly depends on the ratio of phage to bacterial concentrations (multiplicity of infection) at the infection site. Additionally, bacteria can evade phages through the development of phage-resistance and intracellular residence. This review focuses on the use of phage therapy against bacteria that survive within the intracellular niches. Recent research on phage behavior reveals that some phage can directly interact with, get internalized into, and get transcytosed across mammalian cells, prompting further research on the governing mechanisms of these interactions and the feasibility of harnessing therapeutic phage to target intracellular bacteria. Advances to improve the capability of phage attacking intracellular bacteria using formulation approaches such as encapsulating/conjugating phages into/with vector carriers via liposomes, polymeric particles, inorganic nanoparticles, and cell penetrating peptides, are summarized. While promising progress has been achieved, research in this area is still in its infancy and warrants further attention.
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http://dx.doi.org/10.1016/j.addr.2021.113864DOI Listing
July 2021

Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression.

Cell Death Dis 2021 Jul 5;12(7):676. Epub 2021 Jul 5.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Growing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B-miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.
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http://dx.doi.org/10.1038/s41419-021-03911-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257720PMC
July 2021

Carbon neutrality target for G7 economies: Examining the role of environmental policy, green innovation and composite risk index.

J Environ Manage 2021 Jun 30;295:113119. Epub 2021 Jun 30.

School of Economics and Finance, Xi'an Jiaotong University, China. Electronic address:

To achieve zero carbon or achieving carbon neutrality target is of great importance to many countries around the globe especially post Paris climate agreement. This study, unlike previous studies, evaluates the role of environmental policy, green innovation, composite risk index, and renewable energy R&D in achieving carbon neutrality targets for G7 economies from 1990 to 2019. The results confirmed the validity of the EKC hypothesis for G7 economies. Further, the result shows that environmental policy, green innovation, composite risk index, and renewable energy R&D help control carbon emissions. In contrast, income reveals a positive influence on environmental degradation. Furthermore, bidirectional causality has been reported in environmental policy, composite risk index, green innovation, and the CO emissions, while unidirectional causality running from GDP and renewable energy R&D to CO emissions. Based on the empirical findings, it is suggested that environmental policies should be strengthened, promote green innovation and renewable energy research and development expenditures, and political stability and institutional quality must be stabilized to lowers sectoral risks that would help a sustainable environment.
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http://dx.doi.org/10.1016/j.jenvman.2021.113119DOI Listing
June 2021

NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia IL-1β Pathway.

Front Immunol 2021 15;12:661939. Epub 2021 Jun 15.

Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.

NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inflammasome in acute myeloid leukemia (AML) remains unclear. We showed that NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, which is correlated with poor prognosis. The activation of NLRP3 inflammasome in AML cells promotes leukemia cells proliferation, inhibits apoptosis and increases resistance to chemotherapy, while inactivation of NLRP3 by caspase-1 or NF-κB inhibitor shows leukemia-suppressing effects. Bayesian networks analysis and cell co-culture tests further suggest that NLRP3 inflammasome acts through IL-1β but not IL-18 in AML. Knocking down endogenous IL-1β or anti-IL-1β antibody inhibits leukemia cells whereas IL-1β cytokine enhances leukemia proliferation. In AML murine model, up-regulation of NLRP3 increases the leukemia burden in bone marrow, spleen and liver, and shortens the survival time; furthermore, knocking out NLRP3 inhibits leukemia progression. Collectively, all these evidences demonstrate that NLRP3 inflammasome promotes AML progression in an IL-1β dependent manner, and targeting NLRP3 inflammasome may provide a novel therapeutic option for AML.
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http://dx.doi.org/10.3389/fimmu.2021.661939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239362PMC
June 2021

Arachidonic Acid Metabolism Controls Macrophage Alternative Activation Through Regulating Oxidative Phosphorylation in PPARγ Dependent Manner.

Front Immunol 2021 3;12:618501. Epub 2021 Jun 3.

NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing, China.

Macrophage polarization is mainly steered by metabolic reprogramming in the tissue microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophage polarization models, we revealed a pivotal role for arachidonic acid metabolism in determining the phenotype of M2 macrophages. We demonstrated that macrophage M2 polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARγ bridges these two seemingly unrelated processes modulating oxidative phosphorylation (OXPHOS). Through inhibiting PPARγ, PGE2 enhanced OXPHOS, resulting in the alternative activation of macrophages, which was counterweighted by the activation of PPARγ. This connection between PGE2 biosynthesis and macrophage M2 polarization also existed in human and mouse esophageal squamous cell carcinoma. Our results highlight the critical role of arachidonic acid and metabolic PGE2 as immune regulators in modulating tissue homeostasis and pathological process.
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http://dx.doi.org/10.3389/fimmu.2021.618501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211451PMC
June 2021

Discovery of TMPRSS2 Inhibitors from Virtual Screening as a Potential Treatment of COVID-19.

ACS Pharmacol Transl Sci 2021 Jun 2;4(3):1124-1135. Epub 2021 Apr 2.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted researchers to pivot their efforts to finding antiviral compounds and vaccines. In this study, we focused on the human host cell transmembrane protease serine 2 (TMPRSS2), which plays an important role in the viral life cycle by cleaving the spike protein to initiate membrane fusion. TMPRSS2 is an attractive target and has received attention for the development of drugs against SARS and Middle East respiratory syndrome. Starting with comparative structural modeling and a binding model analysis, we developed an efficient pharmacophore-based approach and applied a large-scale in silico database screening for small-molecule inhibitors against TMPRSS2. The hits were evaluated in the TMPRSS2 biochemical assay and the SARS-CoV-2 pseudotyped particle entry assay. A number of novel inhibitors were identified, providing starting points for the further development of drug candidates for the treatment of coronavirus disease 2019.
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http://dx.doi.org/10.1021/acsptsci.0c00221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043206PMC
June 2021

Generation of Alagille syndrome derived induced pluripotent stem cell line carrying heterozygous mutation in the JAGGED-1 gene at splicing site (Chr20: 10,629,709C>A) before exon 11.

Stem Cell Res 2021 05 27;53:102366. Epub 2021 Apr 27.

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Alagille syndrome (ALGS) is a multisystem autosomal dominant disorder caused by defects in the Notch signaling pathway, including the mutation in JAGGED1 (JAG1) (ALGS type 1) or NOTCH2 (ALGS type 2). An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 3-month-old patient with heterozygous mutation at JAG1 splicing site (Chr20: 10,629,709C>A) before exon 11. This iPSC model offers a useful resource for disease modeling to study the disease pathophysiology and to develop therapeutics for treatment of ALGS.
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http://dx.doi.org/10.1016/j.scr.2021.102366DOI Listing
May 2021

The first Chinese national standards for SARS-CoV-2 neutralizing antibody.

Vaccine 2021 06 19;39(28):3724-3730. Epub 2021 May 19.

Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China. Electronic address:

In order to meet the domestic urgent needs of evaluating the immunogenicity of vaccines and the potency testing of therapeutic antibody products against coronavirus disease 2019 (COVID-19), the first Chinese national standards for SARS-CoV-2 neutralizing antibody were established. The potency and stability of the candidate standards were determined by neutralization assay and accelerated degradation study. The stability studies showed that the standards were stable in the short-term. The collaborative study showed that the candidate standards could reduce the variations in neutralization titers between labs and thus improve comparability of neutralizing antibody measurements. Sample 22 has been approved by the Biological Product Reference Standards Sub-Committee of the National Drug Reference Standards Committee as the first Chinese National Standard for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralizing antibody, with an assigned potency of 1,000 units per milliliter (U/ml). This standard will contribute to the standardized assessment of the quality and efficacy of vaccines and therapeutics for COVID-19 in China.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133612PMC
June 2021

An induced pluripotent stem cell line (NCATS-CL9075) from a patient carrying compound heterozygote mutations, p.R390P and p.L318P, in the NGLY1 gene.

Stem Cell Res 2021 Jul 20;54:102400. Epub 2021 May 20.

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. Electronic address:

NGLY1 deficiency is a rare disorder caused by mutations in the NGLY1 gene which codes for the highly conserved N-glycanase1 (NGLY1). This enzyme functions in cytosolic deglycosylation of N- linked glycoproteins. An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 2-year-old patient carrying compound heterozygous mutations, p.R390P and p.L318P in the NGLY1 gene. This cell-based iPSC disease model provides a resource to study disease pathophysiology and to develop a cell-based disease model for drug development for NGLY1 patients.
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http://dx.doi.org/10.1016/j.scr.2021.102400DOI Listing
July 2021

Sensitivity, specificity, and safety of a novel ESAT6-CFP10 skin test for tuberculosis infection in China: two randomized, self-controlled, parallel-group phase 2b trials.

Clin Infect Dis 2021 May 22. Epub 2021 May 22.

Center for Disease Control and Prevention of Jiangsu Province, Nanjing, Jiangsu Province, PR, China.

Background: Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of the novel ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults.

Methods: We conducted two randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A Bacillus Calmette Guerin (BCG) model was also established to assess the diagnosis of tuberculosis infection using EC skin test.

Results: In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive the EC skin test at 1.0μg/0.1ml or 0.5μg/0.1ml. The area under the curve was 0.95 (95% CI, 0.91-0.97) from the EC skin test at a dose of 1.0μg/0.1ml at 24-72 hours. Compared to the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI 77.8-97.2 versus 86.5, 95% CI 79.5-93.4) and specificity (98.9, 95% CI 96.0-99.9 versus 96.1, 95% CI 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed.

Conclusions: The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0μg/0.1ml, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination.
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http://dx.doi.org/10.1093/cid/ciab472DOI Listing
May 2021

COVID-19 vaccines: progress and understanding on quality control and evaluation.

Signal Transduct Target Ther 2021 05 18;6(1):199. Epub 2021 May 18.

National Institutes for Food and Drug Control, Beijing, China.

The outbreak of COVID-19 has posed a huge threat to global health and economy. Countermeasures have revolutionized norms for working, socializing, learning, and travel. Importantly, vaccines have been considered as most effective tools to combat with COVID-19. As of the beginning of 2021, >200 COVID-19 vaccine candidates, covering nearly all existing technologies and platforms, are being research and development (R&D) by multiple manufacturers worldwide. This has posed a huge obstacle to the quality control and evaluation of those candidate vaccines, especially in China, where five vaccine platforms are deployed in parallel. To accelerate the R&D progress of COVID-19 vaccines, the guidances on R&D of COVID-19 vaccine have been issued by National Regulatory Authorities or organizations worldwide. The Center for Drug Evaluation and national quality control laboratory in China have played a leading role in launching the research on quality control and evaluation in collaboration with relevant laboratories involved in the vaccine R&D, which greatly supported the progression of vaccines R&D, and accelerated the approval for emergency use and conditional marketing of currently vaccine candidates. In this paper, the progress and experience gained in quality control and evaluation of COVID-19 vaccines developed in China are summarized, which might provide references for the R&D of current and next generation of COVID-19 vaccines worldwide.
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http://dx.doi.org/10.1038/s41392-021-00621-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129697PMC
May 2021

GPIbα is the driving force of hepatic thrombopoietin generation.

Res Pract Thromb Haemost 2021 May 3;5(4):e12506. Epub 2021 May 3.

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada.

Thrombopoietin (TPO), a glycoprotein hormone produced predominantly in the liver, plays important roles in the hematopoietic stem cell (HSC) niche, and is essential for megakaryopoiesis and platelet generation. Long-standing understanding proposes that TPO is constitutively produced by hepatocytes, and levels are fine-tuned through platelet and megakaryocyte internalization/degradation via the c-Mpl receptor. However, in immune thrombocytopenia (ITP) and several other diseases, TPO levels are inconsistent with this theory. Recent studies showed that platelets, besides their TPO clearance, can induce TPO production in the liver. Our group also accidentally discovered that platelet glycoprotein (GP) Ibα is required for platelet-mediated TPO generation, which is underscored in both GPIbα mice and patients with Bernard-Soulier syndrome. This review will introduce platelet versatilities and several new findings in hemostasis and platelet consumption but focus on its roles in TPO regulation. The implications of these new discoveries in hematopoiesis and the HSC niche, particularly in ITP, will be discussed.
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http://dx.doi.org/10.1002/rth2.12506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105161PMC
May 2021

Human activities can drive sulfate-reducing bacteria community in Chinese intertidal sediments by affecting metal distribution.

Sci Total Environ 2021 Sep 3;786:147490. Epub 2021 May 3.

Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China; State Key Laboratory of Estuarine and Coastal Research, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China; Shanghai Key Lab for Urban Ecological Processes and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China; Yangtze Delta Estuarine Wetland Ecosystem Observation and Research Station, Ministry of Education & Shanghai, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China. Electronic address:

Sulfate-reducing bacteria (SRB), which are ubiquitous in intertidal sediments, play an important role in global sulfur and carbon cycles, and in the bioremediation of toxic metalloids/metals. Pollution from human activities is now a major challenge to the sustainable development of the intertidal zone, but little is known about how and to what extent various anthropic and/or natural factors affect the SRB community. In the current study, based on the dsrB gene, we investigated the SRB community in intertidal sediment along China's coastline. The results showed that dsrB gene abundances varied among different sampling sites, with the highest average abundance of SRB at XHR (near the Bohai Sea). The SRB community structures showed obvious spatial distribution patterns with latitude along the coastal areas of China, with Desulfobulbus generally being the dominant genus. Correlation analysis and redundancy discriminant analysis revealed that total organic carbon (TOC) and pH were significantly correlated with the richness of the SRB community, and salinity, pH, sulfate and climatic parameters could be the important natural factors influencing the composition of the SRB community. Moreover, metals, especially bioavailable metals, could regulate the diversity and composition of the SRB communities. Importantly, according to structural equation model (SEM) analysis, anthropic factors (e.g., population, economy and industrial activities) could drive SRB community diversity directly or by significantly affecting the concentrations of metals. This study provides the first comprehensive investigation of the direct and indirect anthropic factors on the SRB community in intertidal sediments on a continental scale.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147490DOI Listing
September 2021

High-throughput protein modification quantitation analysis using intact protein MRM and its application on hENGase inhibitor screening.

Talanta 2021 Aug 1;231:122384. Epub 2021 Apr 1.

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA. Electronic address:

Proteins are widely used as drug targets, enzyme substrates, and biomarkers for numerous diseases. The emerging demand for proteins quantitation has been increasing in multiple fields. Currently, there is still a big gap for high-throughput protein quantitation at intact protein level using label-free method. Here we choose ribonuclease B (RNB) as a model, which is the substrate for human endo-β-N-acetylglucosaminidase (hENGase), a promising drug target for the treatment of N-Glycanase deficiency. Intact proteinlevel multiple reaction monitoring (MRM) methods were initally developed and optimized to quantify RNB and deglycosylated RNB (RNB-deg), with the S/N ratio improved by nearly 20-fold compared to the traditional full MS scan methods. To further increase the throughput making it possible for hENGase inhibitors screen, the protein MRM methods were introduced to the RapidFire-MS/MS system, achieving at least 12-fold throughput improvement. This assay was further optimized into 384-well plate format for compound screening with S/B ratio >37-fold and Z' factor >0.7 that is suitable for high-throughput screening of compound collections with a speed of 2 h per 384-well plate and an ability to screen over 3000 compounds per day at a single concentration dose. This 384-well plate based automated SPE-MS/MS assay is efficient and robust for compound screening and the assay format has a wide applicability to protein targets for other disease models.
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http://dx.doi.org/10.1016/j.talanta.2021.122384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215893PMC
August 2021

COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations.

Front Immunol 2021 12;12:669339. Epub 2021 Apr 12.

National Institutes for Food and Drug Control, Beijing, China.

The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.
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http://dx.doi.org/10.3389/fimmu.2021.669339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071852PMC
May 2021

A Pilot Study on EEG-Based Evaluation of Visually Induced Motion Sickness.

J Imaging Sci Technol 2020 Mar 31;64(2):205011-2050110. Epub 2020 Jan 31.

Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

The most prominent problem in virtual reality (VR) technology is that users may experience motion sickness-like symptoms when they immerse into a VR environment. These symptoms are recognized as visually induced motion sickness (VIMS) or virtual reality motion sickness (VRMS). The objectives of this study were to investigate the association between the electroencephalogram (EEG) and subjectively rated VIMS level (VIMSL) and find the EEG markers for VIMS evaluation. In this study, a VR-based vehicle-driving simulator (VDS) was used to induce VIMS symptoms, and a wearable EEG device with four electrodes, the Muse, was used to collect EEG data of subjects. Our results suggest that individual tolerance, susceptibility, and recoverability to VIMS varied largely among subjects; the following markers were shown to be significantly different from no-VIMS and VIMS states (P < 0.05): (1) Means of gravity frequency (GF) for [email protected], [email protected], [email protected], [email protected], and [email protected]; (2) Standard deviation of GF for [email protected], [email protected], [email protected], [email protected], and [email protected](FP2-FP1); (3) Standard deviation of power spectral entropy (PSE) for FP1; (4) Means of Kolmogorov complexity (KC) for TP9, FP1, and FP2. These results also demonstrate that it is feasible to perform VIMS evaluation using an EEG device with a small number of electrodes.
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http://dx.doi.org/10.2352/J.ImagingSci.Technol.2020.64.2.020501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075303PMC
March 2020

Effects of SARS-CoV-2 variants on vaccine efficacy and response strategies.

Expert Rev Vaccines 2021 04 14;20(4):365-373. Epub 2021 Apr 14.

Institute of Biological Products, Division of Hepatitis and Enterovirus Vaccines, National Institutes for Food and Drug Control, Beijing, China.

Introduction: As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread, several variants have emerged. Variants B.1.1.7 and B.1.351 have attracted significant attention owing to their widespread transmission and possible immune evasion. A total of 19 SARS-CoV-2 vaccines based on original strains have entered clinical studies, including nine vaccines that have obtained emergency use or conditional marketing authorizations. However, newly emerging variants may affect their protective efficacy. Decreased efficacy of the Novartis, Johnson & Johnson, and AstraZeneca vaccines against B.1.351 has been reported. The spread of variants creates a tremendous challenge for the prevention and control of the SARS-CoV-2 pandemic via vaccination. Several response strategies, including accelerating massive rollouts of current vaccines, increasing vaccine immunogenicity by increasing vaccination doses, and accelerating next-generation vaccines against variants, have been suggested.

Areas Covered: SARS-CoV-2 vaccine efficacy against variants and response strategies for emerging variants.

Expert Opinion: Current SARS-CoV-2 vaccines authorized for emergency use or under clinical trials have shown certain advantages in providing adequate protection against new variants. We analyzed the effects of reported variants on neutralizing antibodies and the protective efficacy of different vaccines and propose strategies for applying current vaccines against variants and developing next-generation vaccines.
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http://dx.doi.org/10.1080/14760584.2021.1903879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054487PMC
April 2021

Identification of SARS-CoV-2 viral entry inhibitors using machine learning and cell-based pseudotyped particle assay.

Bioorg Med Chem 2021 05 26;38:116119. Epub 2021 Mar 26.

National Center for Advancing Translational Sciences (NCATS), 9800 Medical Center Dr., Rockville, MD 20850, USA. Electronic address:

In response to the pandemic caused by SARS-CoV-2, we constructed a hybrid support vector machine (SVM) classification model using a set of publicly posted SARS-CoV-2 pseudotyped particle (PP) entry assay repurposing screen data to identify novel potent compounds as a starting point for drug development to treat COVID-19 patients. Two different molecular descriptor systems, atom typing descriptors and 3D fingerprints (FPs), were employed to construct the SVM classification models. Both models achieved reasonable performance, with the area under the curve of receiver operating characteristic (AUC-ROC) of 0.84 and 0.82, respectively. The consensus prediction outperformed the two individual models with significantly improved AUC-ROC of 0.91, where the compounds with inconsistent classifications were excluded. The consensus model was then used to screen the 173,898 compounds in the NCATS annotated and diverse chemical libraries. Of the 255 compounds selected for experimental confirmation, 116 compounds exhibited inhibitory activities in the SARS-CoV-2 PP entry assay with IC values ranged between 0.17 µM and 62.2 µM, representing an enrichment factor of 3.2. These 116 active compounds with diverse and novel structures could potentially serve as starting points for chemistry optimization for COVID-19 drug discovery.
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http://dx.doi.org/10.1016/j.bmc.2021.116119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997310PMC
May 2021

A Comparative Evaluation of Capillary Electrophoresis, Cation-Exchange High-Performance Liquid Chromatography, and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Screening of Hemoglobin Variants.

Am J Clin Pathol 2021 Apr 1. Epub 2021 Apr 1.

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China.

Objectives: The present study was conducted to evaluate the usefulness of capillary electrophoresis (CE), cation-exchange high-performance liquid chromatography (HPLC), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) for the screening of hemoglobin (Hb) variants prevalent in southern China.

Methods: A total of 102 types of Hb variants in 1,083 variant carriers were identified over a 5-year period. These variants were analyzed by a CE method (Capillarys 3 TERA), a cation-exchange HPLC analyzer (Variant II Turbo 2.0), and a MALDI-TOF MS system (QuanTOF).

Results: The presence of 85 (83.3%, 85/102), 84 (82.4%, 84/102), and 62 (60.8%, 62/102) Hb variants was detected by Capillarys 3 TERA, Variant II Turbo 2.0, and QuanTOF, respectively. Of the three methods, only Capillarys 3 TERA recognized all 10 of the most frequent Hb variants in southern China. There were six, two, and three Hb variants that can only be detected by Capillarys 3 TERA, Variant II Turbo 2.0, and QuanTOF, respectively. The detection limit of mass difference for QuanTOF was approximately 11 to 20 Da.

Conclusions: MALDI-TOF MS is suitable for use as an auxiliary method rather than a stand-alone method for the screening of Hb variants prevalent in southern China.
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http://dx.doi.org/10.1093/ajcp/aqaa260DOI Listing
April 2021

Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial.

Lancet Haematol 2021 Apr;8(4):e289-e298

Department of Haematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Primary immune thrombocytopenia is an autoimmune bleeding disorder. Preclinical reports suggest that the sialidase inhibitor oseltamivir induces a platelet response in the treatment of immune thrombocytopenia. This study investigated the activity and safety of dexamethasone plus oseltamivir versus dexamethasone alone as initial treatment in adult patients with primary immune thrombocytopenia.

Methods: This multicentre, randomised, open-label, parallel group, phase 2 trial was done in five tertiary medical hospitals in China. Eligible patients were aged 18 years or older with newly diagnosed, treatment-naive primary immune thrombocytopenia. Participants were randomly assigned (1:1), using block randomisation, to receive either dexamethasone (orally at 40 mg per day for 4 days) plus oseltamivir (orally at 75 mg twice a day for 10 days) or dexamethasone monotherapy (orally at 40 mg a day for 4 days). Patients who did not respond to treatment (platelet counts remained <30 × 10 cells per L or showed bleeding symptoms by day 10) were given an additional cycle of dexamethasone for 4 days in each group. Patients in the dexamethasone plus oseltamivir group who relapsed (platelet counts reduced again to <30 × 10 cells per L) after an initial response were allowed a supplemental course of oseltamivir (75 mg twice a day for 10 days). The coprimary endpoints were 14-day initial overall response and 6-month overall response. Complete response was defined as a platelet count at or above 100 × 10 cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 10 cells per L but less than 100 × 10 cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. A response lasting for at least 6 months without any additional primary immune thrombocytopenia-specific intervention was defined as sustained response. All patients who were randomly assigned and received the allocated intervention were included in the modified intention-to-treat population analysis. This study has been completed and is registered with ClinicalTrials.gov, number NCT01965626.

Findings: From Feb 1, 2016, to May 1, 2019, 120 patients were screened for eligibility, of whom 24 were ineligible and excluded, 96 were enrolled and randomly assigned to receive dexamethasone plus oseltamivir (n=47) or dexamethasone (n=49), and 90 were included in the modified intention-to-treat analysis. Six patients did not receive the allocated intervention. Patients in the dexamethasone plus oseltamivir group had a significantly higher initial response rate (37 [86%] of 43 patients) than did those in the dexamethasone group (31 [66%] of 47 patients; odds ratio [OR] 3·18; 95 CI% 1·13-9·23; p=0·030) at day 14. The 6-month sustained response rate in the dexamethasone plus oseltamivir group was also significantly higher than that in the dexamethasone group (23 [53%] vs 14 [30%]; OR 2·17; 95 CI% 1·16-6·13; p=0·032). During the median follow-up of 8 months (IQR 5-14), two of 90 patients discontinued treatment due to serious adverse events (grade 3); one (2%) patient with general oedema in the dexamethasone plus oseltamivir group and one (2%) patient with fever in the dexamethasone group. The most frequently observed adverse events of any grade were fatigue (five [12%] of 43 in the dexamethasone plus oseltamivir group vs eight [17%] of 47 in the dexamethasone group), gastrointestinal reactions (eight [19%] vs three [6%]), insomnia (seven [16%] vs four [9%]), and anxiety (five [12%] vs three [6%]). There were no grade 4 or 5 adverse events and no treatment-related deaths.

Interpretation: Dexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response.

Funding: National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S2352-3026(21)00030-2DOI Listing
April 2021

Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates.

Emerg Microbes Infect 2021 Dec;10(1):629-637

National Institutes for Food and Drug Control, Beijing, People's Republic of China.

COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.
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http://dx.doi.org/10.1080/22221751.2021.1902245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009122PMC
December 2021

Antihuman CD44 antibody BJ18 inhibits platelet phagocytosis by correcting aberrant FcɣR expression and M1 polarization in immune thrombocytopenia.

Int Immunopharmacol 2021 Jun 6;95:107502. Epub 2021 Mar 6.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China. Electronic address:

Background: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease with a low platelet count. CD44 is a pivotal component involved in phagocytosis and inflammation, and monoclonal antibodies (mAbs) against CD44 have been shown to be beneficial in several autoimmune diseases. In the present study, we investigated the correlation between CD44 levels and disease severity in patients with ITP and explored the immunomodulatory mechanisms of the antihuman CD44 mAb BJ18 on platelet phagocytosis mediated by monocytes/macrophages.

Methods: Plasma was collected from 45 participants to measure the circulating concentration of CD44 using ELISA. Peripheral blood mononuclear cells from patients and controls were isolated and induced to differentiate into monocytes/macrophages utilizing cytokines and drugs. CD44 expression on circulating cells and the effects of BJ18 on platelet phagocytosis, Fcɣ receptor (FcɣR) expression and M1/M2 polarization of macrophages were evaluated using flow cytometry and qPCR.

Results: CD44 levels of both the soluble form found in plasma and the form expressed on the surface of circulating monocytes/macrophages were significantly elevated in ITP patients. Linear correlations were verified between the CD44 levels and major clinical characteristics. In an in vitro study, BJ18 successfully inhibited platelet phagocytosis by monocytes/macrophages obtained from ITP patients. Further studies indicated that BJ18 corrected abnormal FcγR expression on monocytes/macrophages. Moreover, the polarization of proinflammatory M1 macrophages could also be regulated by BJ18.

Conclusions: Our data indicated that the CD44 level has potential predictive value for disease severity and that the antihuman CD44 mAb BJ18 may be a promising therapy for ITP patients.
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http://dx.doi.org/10.1016/j.intimp.2021.107502DOI Listing
June 2021

Application of niclosamide and analogs as small molecule inhibitors of Zika virus and SARS-CoV-2 infection.

Bioorg Med Chem Lett 2021 05 6;40:127906. Epub 2021 Mar 6.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3370, USA. Electronic address:

Zika virus has emerged as a potential threat to human health globally. A previous drug repurposing screen identified the approved anthelminthic drug niclosamide as a small molecule inhibitor of Zika virus infection. However, as antihelminthic drugs are generally designed to have low absorption when dosed orally, the very limited bioavailability of niclosamide will likely hinder its potential direct repurposing as an antiviral medication. Here, we conducted SAR studies focusing on the anilide and salicylic acid regions of niclosamide to improve physicochemical properties such as microsomal metabolic stability, permeability and solubility. We found that the 5-bromo substitution in the salicylic acid region retains potency while providing better drug-like properties. Other modifications in the anilide region with 2'-OMe and 2'-H substitutions were also advantageous. We found that the 4'-NO substituent can be replaced with a 4'-CN or 4'-CF substituents. Together, these modifications provide a basis for optimizing the structure of niclosamide to improve systemic exposure for application of niclosamide analogs as drug lead candidates for treating Zika and other viral infections. Indeed, key analogs were also able to rescue cells from the cytopathic effect of SARS-CoV-2 infection, indicating relevance for therapeutic strategies targeting the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.bmcl.2021.127906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936759PMC
May 2021

Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV Infection.

Nano Lett 2021 03 8;21(6):2476-2486. Epub 2021 Mar 8.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.

Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D-LS and gp350D-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D. Overall, these results support gp350D-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.
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http://dx.doi.org/10.1021/acs.nanolett.0c04687DOI Listing
March 2021

T cell epitope screening of Epstein-Barr virus fusion protein gB.

J Virol 2021 Mar 3. Epub 2021 Mar 3.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

Glycoprotein B (gB) is an essential fusion protein for the Epstein-Barr virus (EBV) infection of both B cells and epithelial cells and is thus a promising target antigen for a prophylactic vaccine to prevent or reduce EBV-associated disease. T cell responses play key roles in the control of persistent EBV infection and in the efficacy of a vaccine. However, to date, T cell responses to gB have been characterized for only a limited number of human leukocyte antigen (HLA) alleles. Here, we screened gB T cell epitopes in 23 healthy EBV carriers and ten patients with nasopharyngeal cancer (NPC) using a peptide library spanning the entire gB sequence. We identified twelve novel epitopes in the context of seven new HLA restrictions that are common in Asian populations. Two epitopes, gB and gB, restricted by HLA-B*58:01 and B*38:02, respectively, elicited specific CD8 T cell responses to inhibit EBV-driven B cell transformation. Interestingly, gB-specific CD8 T cells were more frequent in healthy viral carriers with EBV reactivation than in those without EBV reactivation, indicating that EBV reactivation stimulates both humoral (VCA-gp125-IgA) and cellular responses to gB. We further found that most gB epitopes are conserved among different EBV strains. Our study broadens the diversity and HLA restrictions of gB epitopes and suggests that gB is a common target of T cell responses in healthy viral carriers with EBV reactivation. In particular, the precisely mapped and conserved gB epitopes provide valuable information for prophylactic vaccine development.T cells are crucial for the control of persistent EBV infection and the development of EBV-associated diseases. The EBV gB protein is essential for virus entry into B cells and epithelial cells and is thus a target antigen for vaccine development. Understanding T cell responses to gB is important for subunit vaccine design. Herein, we comprehensively characterized T cell responses to full-length gB. Our results expand the available gB epitopes and HLA restrictions, particularly those common in Asian populations. Furthermore, we showed that gB-specific CD8 T cells inhibit B cell transformation and that gB-specific CD8 T cell responses may be associated with intermittent EBV reactivation in asymptomatic viral carriers. These gB epitopes are highly conserved among geographically separated EBV strains. Precisely mapped and conserved T cell epitopes may contribute to immune monitoring and to the development of a gB subunit vaccine.
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http://dx.doi.org/10.1128/JVI.00081-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139657PMC
March 2021

Interplay of Support, Comparison, and Surveillance in Social Media Weight Management Interventions: Qualitative Study.

JMIR Mhealth Uhealth 2021 03 1;9(3):e19239. Epub 2021 Mar 1.

Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, China.

Background: There has been a significant increase in the trend of using social media as a platform to deliver weight management interventions. This illustrates a need to develop a holistic understanding of doctor-patient communication and peer-to-peer communication in social media interventions and to determine their influences on weight management for people with overweight or obesity. Such studies will highlight how social media can be more effectively integrated into weight management programs to enhance individuals' short-term and long-term weight management behaviors.

Objective: The aim of this study was to examine patients' experiences with doctor-patient communication and peer interactions in a social media-based (WeChat) weight management program, and to describe the interplay of three social influence factors-social support, social comparison, and surveillance-in their weight control practices. The program, designed and implemented by the research team located in a tertiary referral hospital in a southeastern province in China, included both diet and physical activity components that targeted people with overweight or obesity.

Methods: We conducted in-depth interviews with 32 program participants of different ages (mean 35.6, SD 7.7 years), gender (18 women), duration of program membership (mean 1.4 years), and weight loss outcomes (54% weight loss to 9% weight gain). All interview data were audio-recorded, transcribed, and translated using the translation-backtranslation technique. Nvivo software was used to facilitate the coding process.

Results: Results of thematic analysis indicated the distinct functions of professionally led support and peer support. Professional support was presented in the form of knowledge infusion, efficacy enhancement, and provision of timely feedback. Peer support fostered empathy and sense of belonging, and had a mutually reinforcing relationship with peer comparison and peer-based surveillance. Peer comparison enhanced motivation and positive competition. However, it also reinforced negative group norms, and resulted in downturns in reference standards and collective inactivity. Social media surveillance prompted participants' reactions to the gaze from medical professionals and peers that could be encouraging or inhibiting. Surveillance enhanced vigilance with weight control norms; however, its influence weakened when participants chose to fake weight data and turn off notifications. Findings from this study illustrated the interrelated and fluctuating influences of support, comparison, and surveillance.

Conclusions: The interactive traits of social media eased the practices of social support and social comparison, and created new forms of surveillance. This study contributes to an in-depth understanding of social media influences on individuals' weight control behaviors. Practical implications of the study concern improved strategies for maintaining the positive dynamics of social media interactions and preventing negative resistance to surveillance technology.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1900025861; http://www.chictr.org.cn/showprojen.aspx?proj=42497.
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http://dx.doi.org/10.2196/19239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961396PMC
March 2021

Biological activity-based modeling identifies antiviral leads against SARS-CoV-2.

Nat Biotechnol 2021 06 23;39(6):747-753. Epub 2021 Feb 23.

Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, USA.

Computational approaches for drug discovery, such as quantitative structure-activity relationship, rely on structural similarities of small molecules to infer biological activity but are often limited to identifying new drug candidates in the chemical spaces close to known ligands. Here we report a biological activity-based modeling (BABM) approach, in which compound activity profiles established across multiple assays are used as signatures to predict compound activity in other assays or against a new target. This approach was validated by identifying candidate antivirals for Zika and Ebola viruses based on high-throughput screening data. BABM models were then applied to predict 311 compounds with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of the predicted compounds, 32% had antiviral activity in a cell culture live virus assay, the most potent compounds showing a half-maximal inhibitory concentration in the nanomolar range. Most of the confirmed anti-SARS-CoV-2 compounds were found to be viral entry inhibitors and/or autophagy modulators. The confirmed compounds have the potential to be further developed into anti-SARS-CoV-2 therapies.
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http://dx.doi.org/10.1038/s41587-021-00839-1DOI Listing
June 2021

An Integrated Systems Biology Approach Identifies the Proteasome as A Critical Host Machinery for ZIKV and DENV Replication.

Genomics Proteomics Bioinformatics 2021 Feb 18. Epub 2021 Feb 18.

Department of Pharmacology & Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address:

The zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus-host protein-protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for further studies of flavivirus-host interactions, disease pathogenesis, and new drug targets.
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http://dx.doi.org/10.1016/j.gpb.2020.06.016DOI Listing
February 2021

Meningococcal vaccines in China.

Hum Vaccin Immunother 2021 07 10;17(7):2197-2204. Epub 2021 Feb 10.

Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes of Food and Drug Control, Beijing, People's Republic of China.

Meningococcal meningitis caused by is a reportable infectious disease in China, due to the high incidence of meningitis in the era before the availability of vaccines. The disease incidence was markedly reduced after meningococcal vaccination was introduced in the 1980s. Currently, there are polysaccharide, conjugate, and combined vaccine formulations against meningococcal meningitis in the Chinese market, almost all of which are produced by domestic manufacturers. It is necessary to further enhance national meningococcal surveillance to improve the level of prevention and control of meningococcus. However, the immune efficacy and persistence of immunity of vaccines should be monitored. More importantly, additional investments should be made to develop serogroup B meningococcal vaccines.
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http://dx.doi.org/10.1080/21645515.2020.1857201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189055PMC
July 2021
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