Cell Discovery
·
2023
·Vol. 9
·期 1
·1-15
·
IF 33.5
Ai Liangxia,Li Yafei,Zhou Li,Yao Wenrong,Zhang Hao,Hu Zhaoyu,Han Jinyu,Wang Weijie,Wu Junmiao,Xu Pan,Wang Ruiyue,Li Zhangyi,Li Zhouwang,Wei Chengliang,Liang Jianqun,Chen Haobo,Yang Zhimiao,Guo Ming,Huang Zhixiang,Wang Xin,Zhang Zhen,Xiang Wenjie,Sun Dazheng,Xu Lianqiang,Huang Meiyan,Lv Bin,Peng Peiqi,Zhang Shangfeng,Ji Xuhao,Luo Huiyi,Chen Nanping,Chen Jianping,Lan Ke,Hu Yong
Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
·
IF 8.2
Yuting Ren,Peng Ye,Limei Zhang,Jingyang Zhao,Jing Liu,Jiandu Lei,Luying Wang
Considerable research has been devoted to finding a cost-effective chromatographic matrix with efficient adsorption and high throughput. Wood exhibits complex micro-network structures that make it a powerful contender for a novel environment-friendly chromatographic matrix material. We demonstrate a novel strategy to manufacture a wood monolithic column, which chemically modified the wood and imported diethyl aminoethyl, diethylamine, and amino groups. This wood monolithic column can maintain fully monolithic column performances and highly selective to spike glycoprotein of SARS-CoV-2 by ion exchange force. The wood monolithic column was evaluated by static adsorption, dynamic adsorption, and frontal analysis. The results showed that the static adsorption capacity of the wood monolithic column with 2-diethylaminoethylchloride hydrochloride for bovine serum albumin was 14.72 mg/g, and the adsorption process was chemisorption. In addition, it retained 80 % adsorption capacity after 110 repeated adsorption-elution cycles.
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APPLIED PHYSICS LETTERS
·
2023
·Vol. 123
·期 8
·
IF 4
Zhang Qianwen,Wu Huaxiong,Du Yuxiang,Zhang Minghui,Xu Bangqiang,Chen Genqiang,He Shi,Zhang Dan,Li Qi,Wang Hong-Xing
In this study, Au nanoparticles were introduced to functionalize hydrogen-terminated diamond (H-diamond) to optimize surface modification and improve the performance of diamond sensor for trace detection of SARS-CoV-2 N-protein. The Au nanoparticles were obtained by an electron beam evaporation system and annealing. Atom force microscope and scanning electron microscope were utilized to characterize the structure, morphology, and distribution of fabricated Au nanoparticles. The concentration of SARS-CoV-2 N-protein was determined by the investigation of transfer characteristics of a diamond solution gate field effect transistor. Sensitivity of this sensor was obtained as 27.43 mV/lg (N-protein concentration), which was higher than a regular H-diamond sensor. In addition, it had a wider linear detection range of 10 −15 –10 −5 mg/ml and a lower limit of detection of 10 −15 mg/ml. Accordingly, the detection performance of diamond sensor has been greatly improved due to the functionalization of Au nanoparticles.
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Frontiers in Immunology
·
2022
·
IF 8.786
Cheng Jingliang,Fu Jiewen,Tan Qi,Liu Zhiying,Guo Kan,Zhang Lianmei,He Jiayue,Zhou Baixu,Liu Xiaoyan,Li Dabing,Fu Junjiang
ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20−009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.
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ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Yun Chen,Wei Duan,Li Xu,Guanghui Li,Yakun Wan,Henan Li
Until now, COVID-19 caused by SARS-CoV-2 is engulfing the worldwide and still ranging to date, continuing to threaten the public health. The main challenge facing COVID-19 epidemic is short of fast-response and high-efficiency methods to determine SARS-CoV-2 viral pathogens. Herein, a nanobody-based label-free photoelectrochemical (PEC) immunosensor has been fabricated for rapidly detecting SARS-CoV-2 spike protein. As a small-size and high-stability antibody, nanobody was directly and well immobilized with Au nanoparticles and TiO 2 spheres by the interaction. Au deposited TiO 2 nanomaterial possessed 8.5 times photoelectric performance in comparison with TiO 2 in the presence of electron donor owing to surface plasma resonance effect of Au. Based on the steric hindrance effect, this immunoassay platform realized the linear detection from 0.015 to 15000 pg mL −1 , and a limit of detection was low as 5 fg mL −1 . The label-free PEC immunoassay design provides a new idea for convenient, rapid, and efficient test of SARS-CoV-2 spike protein and broadens further application of nanobody as an identification agent to specific biomarkers.
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TALANTA
·
2023
·
IF 6.1
Jingwang Qin,Xiangdong Tian,Siying Liu,Zhengxia Yang,Dawei Shi,Sihong Xu,Yun Zhang
The spread of COVID-19 over the past three years is largely due to the continuous mutation of the virus, which has significantly impeded global efforts to prevent and control this epidemic. Specifically, mutations in the amino acid sequence of the surface spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have directly impacted its biological functions, leading to enhanced transmission and triggering an immune escape effect. Therefore, prompt identification of these mutations is crucial for formulating targeted treatment plans and implementing precise prevention and control measures. In this study, the label-free surface-enhanced Raman scattering (SERS) technology combined with machine learning (ML) algorithms provide a potential solution for accurate identification of SARS-CoV-2 variants. We establish a SERS spectral database of SARS-CoV-2 variants and demonstrate that a diagnostic classifier using a logistic regression (LR) algorithm can provide accurate results within 10 min. Our classifier achieves 100% accuracy for Beta (B.1.351/501Y.V2), Delta (B.1.617), Wuhan (COVID-19) and Omicron (BA.1) variants. In addition, our method achieves 100% accuracy in blind tests of positive and negative human nasal swabs based on the LR model. This method enables detection and classification of variants in complex biological samples. Therefore, ML-based SERS technology is expected to accurately discriminate various SARS-CoV-2 variants and may be used for rapid diagnosis and therapeutic decision-making.
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ADVANCED MATERIALS
·
2021
·Vol. 33
·期 34
·2101707
·
IF 30.849
Min Li,Sanpeng Li,Yixuan Huang,Haixia Chen,Songya Zhang,Zhicheng Zhang,Weigang Wu,Xiaobin Zeng,Boping Zhou,Bin Li
The transfer of foreign synthetic messenger RNA (mRNA) into cells is essential for mRNA-based protein-replacement therapies. Prophylactic mRNA COVID-19 vaccines commonly utilize nanotechnology to deliver mRNA encoding SARS-CoV-2 vaccine antigens, thereby triggering the body's immune response and preventing infections. In this study, a new combinatorial library of symmetric lipid-like compounds is constructed, and among which a lead compound is selected to prepare lipid-like nanoassemblies (LLNs) for intracellular delivery of mRNA. After multiround optimization, the mRNA formulated into core–shell-structured LLNs exhibits more than three orders of magnitude higher resistance to serum than the unprotected mRNA, and leads to sustained and high-level protein expression in mammalian cells. A single intravenous injection of LLNs into mice achieves over 95% mRNA translation in the spleen, without causing significant hematological and histological changes. Delivery of in-vitro-transcribed mRNA that encodes high-affinity truncated ACE2 variants (tACE2v mRNA) through LLNs induces elevated expression and secretion of tACE2v decoys, which is able to effectively block the binding of the receptor-binding domain of the SARS-CoV-2 to the human ACE2 receptor. The robust neutralization activity in vitro suggests that intracellular delivery of mRNA encoding ACE2 receptor mimics via LLNs may represent a potential intervention strategy for COVID-19.
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Advanced Optical Materials
·
2024
·
IF 8
Yingying Wang,Zhonglin Li,Xianglin Li,Kangyu Gao,Zhixiong Yin,Wenjun Liu,Bo Zhong,Guangfeng Kan,Xiaofei Wang,Jie Jiang,Zexiang Shen
Manipulation of wavefront lies at the core of next-generation information technologies. Compared to metal and dielectric metasurfaces, atomic 2D materials exhibit excellent prospects toward fulfilling ultra-thin thickness requirements in flat optics in wavefront shaping, with thickness much smaller than those of traditional bulky devices. However, phase manipulation by light propagating through atomic 2D materials is suppressed due to its sub-nanometer thickness. Here, an approach is reported to realize reflection phase singularities by establishing a zero-reflection point in a monolayer MoS 2 -based multilayer system, which broadens topological study beyond polarization singularity. This is achieved through the creation of a multilayer Fabry-Perot-type interference, and a pronounced phase change in the reflected light is realized due to the high absorption of monolayer MoS 2 in the studied wavelength range. As an application, a rapid, sensitive, and label-free detection of SARS-CoV-2 (2019-nCov) antigen is demonstrated with a detection limit of 10 −12 M L −1 (62 pg ml −1 ) by using monolayer MoS 2 based optical biosensor. In addition to offering a comprehensive study in phase singularity, efficient wavefront engineering based on the reflective system using materials is presented with atomic thickness which may greatly simplify optical architecture in flat optics, and promote its development toward compactness and integrated functions.
研究领域:
光学
·
生物医学工程
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纳米技术
·
材料科学
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Journal of Materials Chemistry B
·
2023
·
IF 7
Yanhao Zhang,Ji Wang,Hanlei Xing,Chao Liu,Wenhui Zha,Shuo Dong,Yuhao Jiang,Xinsong Li
mRNA vaccines have emerged as a highly promising approach for preventing cancer and infectious diseases, attributed to their superior immunogenicity, rapid development speed, and quality-controlled scale production. While homologous mRNA vaccine administration is currently the most prevalent method employed in clinical settings, heterologous administration is a promising avenue worth exploring. In this report, two types of mRNA vaccine formulations for SARS-CoV-2 infection were developed based on different lipid nanoparticle (LNP) delivery systems, and heterologous and homologous mRNA vaccinations were administered to explore the levels of immune responses comparatively. First, five novel H-series ionizable lipids were synthesized and confirmed by NMR and MS. Subsequently, six SARS-CoV-2 receptor-binding domain (RBD) mRNA-encapsulated LNP formulations were prepared using a microfluidic mixer based on H-series and MC3 lipids. These formulations exhibited spherical structures with an average diameter ranging from 90–140 nm, as characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The safety of these formulations was confirmed in vitro by the cytotoxicity assay. Moreover, transfection assay, lysosomal escape test, and western blot, and in vivo biodistribution analyses collectively demonstrated that lipids H03 and MC3 exhibited superior in vitro and in vivo delivery efficacy in comparison to other H-series lipids. Notably, H03-Fluc mRNA exhibited an approximately 2.2-fold higher in vivo bioluminescence signal intensity than MC3-Fluc mRNA. Additionally, evaluation of humoral immunity demonstrated that homologous H03-mRNA vaccination elicited an immune response that was approximately 3-fold higher than that of homologous MC3-mRNA vaccination. More significantly, the heterologous H03-mRNA/MC3-mRNA vaccination elicited an immune response that was approximately 2-3-fold higher than that of homologous H03-mRNA vaccination and 6–9-fold higher than that of homologous MC3-mRNA vaccination, without any observable adverse effects. These results suggest that heterologous mRNA vaccination is superior to homologous mRNA vaccination and may be attributed to differences in LNP carriers. Therefore, our research may inspire further exploration of different delivery systems to enhance mRNA-based therapeutics.
研究领域:
病毒学
·
免疫学
·
药学
·
生物技术
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ACS Sensors
·
2022
·
IF 9.618
Haiyang Yu,Huibin Zhang,Jinhua Li,Zheng Zhao,Minhua Deng,Zhanpeng Ren,Ziqin Li,Chenglong Xue,Mitch Guijun Li,Zhaowei Chen
The disease caused by severe acute respiratory syndrome coronavirus, SARS-CoV-2, is termed COVID-19. Even though COVID-19 has been out for more than two years, it is still causing a global pandemic. Due to the limitations of sample collection, transportation, and kit performance, the traditional reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method has a long detection period and high testing costs. An increased risk of infection is inevitable, since many patients may not be diagnosed in time. The CRISPR-Cas13a system can be designed for RNA identification and knockdown, as a promising platform for nucleic acid detection. Here, we designed a solution-gated graphene transistor (SGGT) biosensor based on the CRISPR-Cas13a system. Using the gene-targeting capacity of CRISPR-Cas13a and gate functionalization via multilayer modification, SARS-CoV-2 nucleic acid sequences can be quickly and precisely identified without the need for amplification or fluorescence tagging. The limit of detection (LOD) in both buffer and serum reached the aM level, and the reaction time was about 10 min. The results of the detection of COVID-19 clinical samples from throat swabs agree with RT-PCR. In addition, the interchangeable gates significantly minimize the cost and time of device fabrication. In a nutshell, our biosensor technology is broadly applicable and will be suitable for point-of-care (POC) testing.
研究领域:
生物技术
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纳米技术
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分子生物学
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医学诊断
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Qing Huang,Zefeng Hou,Yunong Zhao,Ruiqin Gu,Chengli Li,Minghong Yang,Huan Liu
Surface plasmon resonance (SPR) technology, boasting prominent advantages including anti-electromagnetic interference, high sensitivity, rapid response, label-free detection, and minimal sample consumption, holds broad application prospects in life sciences, clinical diagnostics, drug screening, and other related fields. However, current optical fiber biochemical sensors are generally plagued by poor probe practicality and stability, low refractive index sensitivity, and inadequate detection capability for ultra-low concentration biomolecules in clinical settings. In this study, we developed a low-cost, high-sensitivity optical fiber SPR biosensor for SARS-CoV-2 antigen detection in the standard sample, employing gold@silver‑platinum (Au@AgPt) core-shell nanospheres as the sensing enhancement module. Au@AgPt core-shell nanospheres possess unique localized surface plasmon resonance (LSPR) properties. When incident light interacts with the nanomaterial surface, it induces a localized electric field enhancement effect. This surface enhancement effect significantly amplifies the optical signal intensity, thereby effectively improving the sensor's detection sensitivity toward the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. This sensing platform achieves fg/mL-level detection sensitivity, excellent linearity, and rapid response performance, offering new technical support for expanding the application of optical fiber sensors in the quantitative detection of ultra-low concentration disease markers.
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Nature Communications
·
2023
·Vol. 14
·期 1
·1-17
·
IF 16.6
Lei Hong,Alu Aqu,Yang Jingyun,He Xi,He Cai,Ren Wenyan,Chen Zimin,Hong Weiqi,Chen Li,He Xuemei,Yang Li,Li Jiong,Wang Zhenling,Wang Wei,Wei Yuquan,Lu Shuaiyao,Lu Guangwen,Song Xiangrong,Wei Xiawei
Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) and a SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization with CCD/RBD-HR induces high levels of antibodies with broad-spectrum neutralization against authentic viruses/pseudoviruses of Omicron-included variants and protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, the intranasal CCD/RBD-HR vaccine also induces potent mucosal immunity as determined by the generation of tissue-resident T cells in the lungs and airway. Moreover, CCD/RBD-HR not only activates professional antigen-presenting cells (APCs), dendritic cells, but also effectively targets nasal epithelial cells, promotes antigen binding via sialic acid, and surprisingly provokes the antigen-presenting of nasal epithelial cells. We demonstrate that CCD is a promising intranasal vaccine adjuvant for provoking strong mucosal immunity and might be a candidate adjuvant for intranasal vaccine development for many types of infectious diseases, including COVID-19.
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