26 results on '"Naru ZHANG"'
Search Results
2. Advancement in the Development of Therapeutics Against Zika Virus Infection
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Kangchen Li, Qianting Ji, Shibo Jiang, and Naru Zhang
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Zika virus ,pathogenesis ,therapeutics ,NS2B–NS3 protease inhibitors ,NS3 protease inhibitors ,NS5 protease inhibitors ,Microbiology ,QR1-502 - Abstract
Zika virus (ZIKV), a re-emerging arbovirus, causes teratogenic effects on the fetus and normal nerve functions, resulting in harmful autoimmune responses, which call for the development of therapeutics against ZIKV infection. In this review, we introduce the pathogenesis of ZIKV infection and summarize the advancement in the development of therapeutics against ZIKV infection. It provides guidance for the development of effective therapeutics against ZIKV infection.
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- 2022
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3. A Perspective on the Roles of Adjuvants in Developing Highly Potent COVID-19 Vaccines
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Naru Zhang, Kangchen Li, Zezhong Liu, Kutty Selva Nandakumar, and Shibo Jiang
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COVID-19 ,SARS-CoV-2 ,variants ,vaccine ,adjuvant ,Microbiology ,QR1-502 - Abstract
Several countries have made unremitting efforts to develop an optimal vaccine in the fight against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the increasing occurrence of SARS-CoV-2 variants, current vaccines show decreased neutralizing activities, especially towards the Omicron variant. In this context, adding appropriate adjuvants to COVID-19 vaccines can substantially reduce the number of required doses and improve efficacy or cross-neutralizing protection. We mainly focus on research progress and achievements associated with adjuvanted COVID-19 subunit and inactivated vaccines. We further compare the advantages and disadvantages of different adjuvant formulations in order to provide a scientific reference for designing an effective strategy for future vaccine development.
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- 2022
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4. Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant
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Naru Zhang, Qianting Ji, Zezhong Liu, Kaiming Tang, Yubin Xie, Kangchen Li, Jie Zhou, Sisi Li, Haotian Shang, Zecan Shi, Tianyu Zheng, Jiawei Yao, Lu Lu, Shuofeng Yuan, and Shibo Jiang
- Subjects
COVID-19 ,SARS-CoV-2 ,variants ,aluminum ,nanoparticle manganese ,MF59 ,Microbiology ,QR1-502 - Abstract
The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.
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- 2022
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5. Current Progress in the Development of Zika Virus Vaccines
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Kehui Zhou, Chaoqun Li, Wen Shi, Xiaodan Hu, Kutty Selva Nandakumar, Shibo Jiang, and Naru Zhang
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Zika virus ,vaccine ,different strategies ,Medicine - Abstract
Zika virus (ZIKV) is an arbovirus first discovered in the Americas. ZIKV infection is insidious based on its mild clinical symptoms observed after infection. In Brazil, after 2015, ZIKV infection broke out on a large scale, and many infected pregnant women gave birth to babies with microcephaly. The teratogenic effects of the virus on the fetus and its effects on nerves and the immune system have attracted great attention. Currently, no specific prophylactics or therapeutics are clinically available to treat ZIKV infection. Development of a safe and effective vaccine is essential to prevent the rise of any potential pandemic. In this review, we summarize the latest research on Zika vaccine development based on different strategies, including DNA vaccines, subunit vaccines, live-attenuated vaccines, virus-vector-based vaccines, inactivated vaccines, virus-like particles (VLPs), mRNA-based vaccines, and others. We anticipate that this review will facilitate further progress toward the development of effective and safe vaccines against ZIKV infection.
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- 2021
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6. Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines
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Naru Zhang, Chaoqun Li, Shibo Jiang, and Lanying Du
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flaviviruses ,Zika virus ,Dengue virus ,West Nile virus ,Japanese encephalitis virus ,virus-like particles ,Medicine - Abstract
Flaviviruses include several medically important viruses, such as Zika virus (ZIKV), Dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). They have expanded in geographic distribution and refocused international attention in recent years. Vaccination is one of the most effective public health strategies for combating flavivirus infections. In this review, we summarized virus-like particle (VLP)-based vaccines against the above four mentioned flaviviruses. Potential strategies to improve the efficacy of VLP-based flavivirus vaccines were also illustrated. The applications of flavivirus VLPs as tools for viral detection and antiviral drug screening were finally proposed.
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- 2020
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7. Development of Small-Molecule MERS-CoV Inhibitors
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Ruiying Liang, Lili Wang, Naru Zhang, Xiaoqian Deng, Meng Su, Yudan Su, Lanfang Hu, Chen He, Tianlei Ying, Shibo Jiang, and Fei Yu
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MERS-CoV ,mechanism of action ,small-molecule inhibitor ,Microbiology ,QR1-502 - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection.
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- 2018
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8. An overview of Middle East respiratory syndrome coronavirus vaccines in preclinical studies
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Lanying Du, Jian Shang, Naru Zhang, Chaoqun Li, and Kehui Zhou
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Models, Molecular ,0301 basic medicine ,2019-20 coronavirus outbreak ,Middle East respiratory syndrome coronavirus ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Viral Nonstructural Proteins ,medicine.disease_cause ,Article ,03 medical and health sciences ,Immunogenicity, Vaccine ,0302 clinical medicine ,Drug Discovery ,medicine ,Humans ,030212 general & internal medicine ,Coronavirus ,Pharmacology ,business.industry ,Viral Vaccine ,High mortality ,virus diseases ,Spike Protein ,Viral Vaccines ,Virology ,030104 developmental biology ,Spike Glycoprotein, Coronavirus ,Middle East Respiratory Syndrome Coronavirus ,Molecular Medicine ,Coronavirus Infections ,business - Abstract
INTRODUCTION: Middle East respiratory syndrome coronavirus (MERS-CoV) causes high mortality in humans. No vaccines are approved for use in humans; therefore, a consistent effort to develop safe and effective MERS vaccines is needed. AREAS COVERED: This review describes the structure of MERS-CoV and the function of its proteins, summarizes MERS vaccine candidates under preclinical study (based on spike and non-spike structural proteins, inactivated virus, and live-attenuated virus), and highlights potential problems that could prevent these vaccines entering clinical trials. It provides guidance for the development of safe and effective MERS-CoV vaccines. EXPERT OPINION: Although many MERS-CoV vaccines have been developed, most remain at the preclinical stage. Some vaccines demonstrate immunogenicity and efficacy in animal models, while others have potential adverse effects or low efficacy against high-dose or divergent virus strains. Novel strategies are needed to design safe and effective MERS vaccines to induce broad-spectrum immune responses and improve protective efficacy against multiple strains of MERS-CoV and MERS-like coronaviruses with pandemic potential. More funds should be invested to move vaccine candidates into human clinical trials.
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- 2020
9. Recent advances in the detection of respiratory virus infection in humans
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Yudan Su, Meng Su, Jing Ren, Xiaoqian Deng, Naru Zhang, Ruiying Liang, Shibo Jiang, Fei Yu, Lili Wang, Chen He, Lanfang Hu, and Lanying Du
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Rhinovirus ,viruses ,respiratory syncytial virus ,coronavirus ,Reviews ,Respiratory Syncytial Virus Infections ,Review ,Immunologic Tests ,medicine.disease_cause ,Real-Time Polymerase Chain Reaction ,Virus ,influenza virus ,Adenovirus Infections, Human ,03 medical and health sciences ,0302 clinical medicine ,COVID-19 Testing ,Virology ,Influenza, Human ,medicine ,Humans ,030212 general & internal medicine ,respiratory viral infection ,Respiratory Tract Infections ,Coronavirus ,Immunoassay ,Picornaviridae Infections ,Respiratory tract infections ,business.industry ,Clinical Laboratory Techniques ,diagnostic methods ,Nucleic acid amplification technique ,adenovirus ,medicine.disease ,medicine.anatomical_structure ,Infectious Diseases ,Viruses ,Respiratory virus ,030211 gastroenterology & hepatology ,business ,Coronavirus Infections ,Pneumonia (non-human) ,Multiplex Polymerase Chain Reaction ,Nucleic Acid Amplification Techniques ,Respiratory tract - Abstract
Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019‐nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray‐based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections., Research Highlights Respiratory tract viral infection including 2019‐nCoV poses great threats worldwide. Currently available and novel emerging diagnostic methods are summarized for several common respiratory viruses, including influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. This review is aimed to assist researchers and clinicians to develop timely and effective diagnostic strategies to detect respiratory virus infections.
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- 2020
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10. Current Progress in the Development of Zika Virus Vaccines
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Naru Zhang, Wen Shi, Kutty Selva Nandakumar, Kehui Zhou, Shibo Jiang, Xiaodan Hu, and Chaoqun Li
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Microcephaly ,Immunology ,Review ,Arbovirus ,Virus ,Zika virus ,DNA vaccination ,Immune system ,vaccine ,Drug Discovery ,Pandemic ,medicine ,Pharmacology (medical) ,Subunit vaccines ,Pharmacology ,biology ,business.industry ,biology.organism_classification ,medicine.disease ,Virology ,Infectious Diseases ,Medicine ,business ,different strategies - Abstract
Zika virus (ZIKV) is an arbovirus first discovered in the Americas. ZIKV infection is insidious based on its mild clinical symptoms observed after infection. In Brazil, after 2015, ZIKV infection broke out on a large scale, and many infected pregnant women gave birth to babies with microcephaly. The teratogenic effects of the virus on the fetus and its effects on nerves and the immune system have attracted great attention. Currently, no specific prophylactics or therapeutics are clinically available to treat ZIKV infection. Development of a safe and effective vaccine is essential to prevent the rise of any potential pandemic. In this review, we summarize the latest research on Zika vaccine development based on different strategies, including DNA vaccines, subunit vaccines, live-attenuated vaccines, virus-vector-based vaccines, inactivated vaccines, virus-like particles (VLPs), mRNA-based vaccines, and others. We anticipate that this review will facilitate further progress toward the development of effective and safe vaccines against ZIKV infection.
- Published
- 2021
11. Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines
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Chaoqun Li, Naru Zhang, Lanying Du, and Shibo Jiang
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0301 basic medicine ,medicine.drug_class ,viruses ,030106 microbiology ,Immunology ,lcsh:Medicine ,Review ,Dengue virus ,medicine.disease_cause ,virus-like particles ,complex mixtures ,Virus ,Zika virus ,03 medical and health sciences ,Virus-like particle ,Drug Discovery ,medicine ,Pharmacology (medical) ,Flavivirus Infections ,Pharmacology ,biology ,lcsh:R ,virus diseases ,Japanese encephalitis ,vaccines ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,Virology ,Flavivirus ,Japanese encephalitis virus ,030104 developmental biology ,Infectious Diseases ,Antiviral drug ,West Nile virus ,flaviviruses - Abstract
Flaviviruses include several medically important viruses, such as Zika virus (ZIKV), Dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). They have expanded in geographic distribution and refocused international attention in recent years. Vaccination is one of the most effective public health strategies for combating flavivirus infections. In this review, we summarized virus-like particle (VLP)-based vaccines against the above four mentioned flaviviruses. Potential strategies to improve the efficacy of VLP-based flavivirus vaccines were also illustrated. The applications of flavivirus VLPs as tools for viral detection and antiviral drug screening were finally proposed.
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- 2020
12. Current development of COVID-19 diagnostics, vaccines and therapeutics
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Shibo Jiang, Jintian Liang, Naru Zhang, Chaoqun Li, Kangchen Li, Yue Hu, Lanying Du, and Lili Wang
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0301 basic medicine ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,China ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,viruses ,030106 microbiology ,Immunology ,Pneumonia, Viral ,Therapeutics ,Biology ,medicine.disease_cause ,World Health Organization ,Microbiology ,Antiviral Agents ,Article ,03 medical and health sciences ,Betacoronavirus ,medicine ,Animals ,Humans ,Intensive care medicine ,Diagnostic approaches ,Pandemics ,Coronavirus ,Vaccines ,Clinical Trials as Topic ,SARS-CoV-2 ,virus diseases ,COVID-19 ,Viral Vaccines ,030104 developmental biology ,Infectious Diseases ,Coronavirus Infections - Abstract
A novel coronavirus, designated as SARS-CoV-2, first emerged in Wuhan City, Hubei Province, China, in late December 2019. The rapidly increasing number of cases has caused worldwide panic. In this review, we describe some currently applied diagnostic approaches, as well as therapeutics and vaccines, to prevent, treat and control further outbreaks of SARS-CoV-2 infection.
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- 2020
13. Recent advances in the development of vaccines for chronic inflammatory autoimmune diseases
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Naru Zhang and Kutty Selva Nandakumar
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Male ,0301 basic medicine ,Multiple Sclerosis ,Population ,Autoimmune Diseases ,Arthritis, Rheumatoid ,Epitopes ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Adjuvants, Immunologic ,Vaccines, DNA ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Genetic Predisposition to Disease ,In patient ,education ,Peptide ligand ,Vaccines ,Type 1 diabetes ,education.field_of_study ,High prevalence ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Multiple sclerosis ,Public Health, Environmental and Occupational Health ,Target tissue ,medicine.disease ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,Infectious Diseases ,Rheumatoid arthritis ,Chronic Disease ,Immunology ,Molecular Medicine ,Female ,business ,030215 immunology - Abstract
Chronic inflammatory autoimmune diseases leading to target tissue destruction and disability are not only causing increase in patients' suffering but also contribute to huge economic burden for the society. General increase in life expectancy and high prevalence of these diseases both in elderly and younger population emphasize the importance of developing safe and effective vaccines. In this review, at first the possible mechanisms and risk factors associated with chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D) are discussed. Current advances in the development of vaccines for such autoimmune diseases, particularly those based on DNA, altered peptide ligands and peptide loaded MHC II complexes are discussed in detail. Finally, strategies for improving the efficacy of potential vaccines are explored.
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- 2018
14. The Heat Transfer Characteristics in Stepped Hole of Traditional Metal Materials Induced by Stepped Film Holes
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Libing, Lin, primary, Bo, Zhang, additional, Jiquan, Li, additional, and Naru, Zhang, additional
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- 2020
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15. Development of Small-Molecule MERS-CoV Inhibitors
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Tianlei Ying, Lanfang Hu, Meng Su, Lili Wang, Ruiying Liang, Chen He, Xiaoqian Deng, Shibo Jiang, Naru Zhang, Fei Yu, and Yudan Su
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0301 basic medicine ,medicine.medical_specialty ,Middle East respiratory syndrome coronavirus ,viruses ,lcsh:QR1-502 ,Review ,medicine.disease_cause ,Virus Replication ,Antiviral Agents ,lcsh:Microbiology ,Small Molecule Libraries ,03 medical and health sciences ,Mice ,MERS-CoV ,Virology ,Development economics ,Pandemic ,Drug Discovery ,medicine ,Animals ,Humans ,Pandemics ,Public health ,virus diseases ,respiratory system ,biochemical phenomena, metabolism, and nutrition ,respiratory tract diseases ,030104 developmental biology ,Infectious Diseases ,Middle East Respiratory Syndrome Coronavirus ,Business ,Coronavirus Infections ,small-molecule inhibitor ,mechanism of action - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection.
- Published
- 2018
16. Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis
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Naru Zhang, Rikard Holmdahl, Anna Linusson, Changrong Ge, Johannes Toms, Cecilia M. Lindgren, Mohit Tyagi, Jan Kihlberg, and Johan Viljanen
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musculoskeletal diseases ,Stereochemistry ,T-Lymphocytes ,Molecular Dynamics Simulation ,Major histocompatibility complex ,Protein Structure, Secondary ,Cell Line ,Arthritis, Rheumatoid ,Drug Discovery ,HLA-DR4 Antigen ,Moiety ,Molecule ,Peptide bond ,Humans ,skin and connective tissue diseases ,chemistry.chemical_classification ,biology ,Chemistry ,Hydrogen bond ,Glycopeptide ,Amino acid ,Receptors, TNF-Related Apoptosis-Inducing Ligand ,Intramolecular force ,biology.protein ,Molecular Medicine ,Signal Transduction - Abstract
Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259-273, together with the positioning of the galactose moiety of CII259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.
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- 2018
17. Receptor-binding domain-based subunit vaccines against MERS-CoV
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Lanying Du, Naru Zhang, Lu Lu, Shibo Jiang, and Jian Tang
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Cancer Research ,Middle East respiratory syndrome coronavirus ,viruses ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Drug Discovery ,Pandemic ,medicine ,Animals ,Humans ,Subunit vaccines ,030212 general & internal medicine ,030304 developmental biology ,0303 health sciences ,Viral Vaccine ,virus diseases ,Viral Vaccines ,medicine.disease ,3. Good health ,Infectious Diseases ,Vaccines, Subunit ,Middle East Respiratory Syndrome Coronavirus ,Middle East respiratory syndrome ,Coronavirus Infections - Abstract
Development of effective vaccines, in particular, subunit-based vaccines, against emerging Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) will provide the safest means of preventing the continuous spread of MERS in humans and camels. This review briefly describes the structure of the MERS-CoV spike (S) protein and its receptor-binding domain (RBD), discusses the current status of MERS vaccine development, and illustrates the strategies used to develop RBD-based subunit vaccines against MERS. It also summarizes currently available animal models for MERS-CoV and proposes a future direction for MERS vaccines. Taken together, this review will assist researchers working to develop effective and safe subunit vaccines against MERS-CoV and any other emerging coronaviruses that might cause future pandemics.
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- 2015
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18. Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus
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Rudragouda Channappanavar, Chien Te K. Tseng, Naru Zhang, Lu Lu, Xinrong Tao, Tania Garron, Jian Tang, Shibo Jiang, Stanley Perlman, Yusen Zhou, Cuiqing Ma, Sumaiya Tasneem, Lanying Du, and Lili Wang
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0301 basic medicine ,Middle East respiratory syndrome coronavirus ,medicine.medical_treatment ,Immunology ,MF59 ,Monophosphoryl Lipid A ,Antibodies, Viral ,medicine.disease_cause ,Immunoglobulin G ,MERS-CoV ,Mice ,03 medical and health sciences ,Adjuvants, Immunologic ,MERS ,medicine ,Animals ,Humans ,Immunology and Allergy ,Neutralizing antibody ,Mice, Inbred BALB C ,biology ,business.industry ,Immunogenicity ,Viral Vaccine ,Viral Vaccines ,Virology ,3. Good health ,030104 developmental biology ,Infectious Diseases ,adjuvant effects ,Spike Glycoprotein, Coronavirus ,Vaccines, Subunit ,Middle East Respiratory Syndrome Coronavirus ,biology.protein ,Female ,subunit vaccine ,receptor-binding domain ,Coronavirus Infections ,business ,Adjuvant ,Research Article - Abstract
Middle East respiratory syndrome (MERS), an emerging infectious disease caused by MERS coronavirus (MERS-CoV), has garnered worldwide attention as a consequence of its continuous spread and pandemic potential, making the development of effective vaccines a high priority. We previously demonstrated that residues 377-588 of MERS-CoV spike (S) protein receptor-binding domain (RBD) is a very promising MERS subunit vaccine candidate, capable of inducing potent neutralization antibody responses. In this study, we sought to identify an adjuvant that optimally enhanced the immunogenicity of S377-588 protein fused with Fc of human IgG (S377-588-Fc). Specifically, we compared several commercially available adjuvants, including Freund's adjuvant, aluminum, Monophosphoryl lipid A, Montanide ISA51 and MF59 with regard to their capacity to enhance the immunogenicity of this subunit vaccine. In the absence of adjuvant, S377-588-Fc alone induced readily detectable neutralizing antibody and T-cell responses in immunized mice. However, incorporating an adjuvant improved its immunogenicity. Particularly, among the aforementioned adjuvants evaluated, MF59 is the most potent as judged by its superior ability to induce the highest titers of IgG, IgG1 and IgG2a subtypes, and neutralizing antibodies. The addition of MF59 significantly augmented the immunogenicity of S377-588-Fc to induce strong IgG and neutralizing antibody responses as well as protection against MERS-CoV infection in mice, suggesting that MF59 is an optimal adjuvant for MERS-CoV RBD-based subunit vaccines.
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- 2015
19. Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments—The importance of immunofocusing in subunit vaccine design
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Yang Yang, Chien Te K. Tseng, Fang Li, Lanying Du, Naru Zhang, Cuiqing Ma, Lili Wang, Shibo Jiang, Yusen Zhou, and Xinrong Tao
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Antigenicity ,Protein subunit ,Antibodies, Viral ,Article ,Epitope ,Neutralization Tests ,Animals ,Humans ,Antigens, Viral ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,biology ,Viral Vaccine ,Immunogenicity ,Immunoglobulin Fc Fragments ,Public Health, Environmental and Occupational Health ,Viral Vaccines ,Antibodies, Neutralizing ,Virology ,Protein tertiary structure ,3. Good health ,Infectious Diseases ,Immunoglobulin G ,Spike Glycoprotein, Coronavirus ,Vaccines, Subunit ,Middle East Respiratory Syndrome Coronavirus ,biology.protein ,Receptors, Virus ,Molecular Medicine ,Female ,Rabbits ,Antibody ,Coronavirus Infections ,Receptors, Coronavirus - Abstract
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".
- Published
- 2014
20. Current advancements and potential strategies in the development of MERS-CoV vaccines
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Naru Zhang, Lanying Du, and Shibo Jiang
- Subjects
Middle East respiratory syndrome coronavirus ,viruses ,medicine.medical_treatment ,Immunology ,Biology ,medicine.disease_cause ,Article ,Middle East ,Adjuvants, Immunologic ,Drug Discovery ,medicine ,Animals ,Humans ,Subunit vaccines ,Coronavirus ,Pharmacology ,Viral Vaccine ,Vaccination ,virus diseases ,Viral Vaccines ,medicine.disease ,Virology ,respiratory tract diseases ,3. Good health ,Disease Models, Animal ,Spike Glycoprotein, Coronavirus ,Vaccines, Subunit ,Middle East Respiratory Syndrome Coronavirus ,Emerging infectious disease ,Middle East respiratory syndrome ,Molecular Medicine ,Coronavirus Infections ,Adjuvant - Abstract
Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.
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- 2014
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21. EXPERIMENTAL INVESTIGATION OF GEOMETRICAL EFFECT ON FLOW AND HEAT TRANSFER PERFORMANCE OF LAMILLOY COOLING STRUCTURE.
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Bo ZHANG, Libing LIN, Naru ZHANG, Shuangsong XUE, and Honghu JI
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HEAT transfer ,DISCHARGE coefficient ,COOLING - Abstract
Effect of film hole diameter to discharge coefficients and film cooling effectiveness of the lamilloy were experimentally investigated at the blowing ratios ranging from 0.6 to 2.5. Generally, the cooling effectiveness on the test surface is increased with the film hole diameters and blowing ratios increasing, and the variation tendency along the streamwise through the centerline of film holes also keeps consistent. In the upstream, all configurations have a relatively lower cooling effectiveness, however, with the flows to the downstream, cooling effectiveness grows gradually, and the peak values of effectiveness appeared periodically, the position matches the film hole positions. Besides, between the film holes, fluctuation exists simultaneously. By comparison, the cooling effectiveness and discharge coefficients are both increased with the blowing ratio with same film hole diameters, Moreover, under the same blowing ratios, the cooling effectiveness and discharge coefficients are getting higher when hole diameters increase. [ABSTRACT FROM AUTHOR]
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- 2020
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22. Study on influenza virus-like particles and ssDNA aptamers
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Naru Zhang
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Aptamer ,Biology ,Virology ,Virus ,Microbiology - Published
- 2015
23. Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus
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Guangyu Zhao, Yan Guo, Jian Tang, Chien Te K. Tseng, Lanying Du, Yusen Zhou, Shibo Jiang, Xinrong Tao, and Naru Zhang
- Subjects
Squalene ,Middle East respiratory syndrome coronavirus ,medicine.medical_treatment ,Recombinant Fusion Proteins ,Immunology ,MF59 ,Polysorbates ,medicine.disease_cause ,Antibodies, Viral ,Immune system ,Antigen ,Adjuvants, Immunologic ,medicine ,Immunology and Allergy ,Animals ,Humans ,Neutralizing antibody ,Antigens, Viral ,Pharmacology ,Immunity, Cellular ,Mice, Inbred BALB C ,biology ,Viral Vaccines ,medicine.disease ,Virology ,Antibodies, Neutralizing ,3. Good health ,Immunity, Humoral ,Immunoglobulin Fc Fragments ,Vaccines, Subunit ,biology.protein ,Middle East Respiratory Syndrome Coronavirus ,Middle East respiratory syndrome ,Female ,Antibody ,Coronavirus Infections ,Adjuvant ,Research Paper - Abstract
Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377–588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.
- Published
- 2015
24. Cross-protection of influenza A virus infection by a DNA aptamer targeting the PA endonuclease domain
- Author
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Naru Zhang, Hin Chu, Billy K. C. Chow, Shuofeng Yuan, Bo-Jian Zheng, Huiping Shuai, Jie Zhou, and Kailash Singh
- Subjects
Insecta ,Aptamer ,Cross Protection ,DNA Footprinting ,Oligonucleotides ,Biology ,Calorimetry ,medicine.disease_cause ,Antiviral Agents ,Virus ,Protein Structure, Secondary ,Cell Line ,Madin Darby Canine Kidney Cells ,Endonuclease ,Dogs ,Species Specificity ,Influenza, Human ,Influenza A virus ,medicine ,Animals ,Deoxyribonuclease I ,Humans ,Pharmacology (medical) ,Polymerase ,Pharmacology ,Influenza A Virus, H5N1 Subtype ,SELEX Aptamer Technique ,Aptamers, Nucleotide ,Endonucleases ,Virology ,Molecular biology ,Infectious Diseases ,biology.protein ,Systematic evolution of ligands by exponential enrichment - Abstract
Amino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PANis highly conserved among different subtypes of influenza virus, which suggests PANto be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PANdomain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation ofin vitroendonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PANwere selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs.
- Published
- 2015
25. Advancements in the development of subunit influenza vaccines
- Author
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Bo-Jian Zheng, Lu Lu, Yusen Zhou, Naru Zhang, Lanying Du, and Shibo Jiang
- Subjects
Viral matrix protein ,biology ,Protein subunit ,Immunology ,virus diseases ,Hemagglutinin (influenza) ,medicine.disease_cause ,Microbiology ,Virology ,H5N1 genetic structure ,Article ,Nucleoprotein ,Influenza virus matrix protein 2 ,Infectious Diseases ,Influenza A virus ,Influenza Vaccines ,Vaccines, Subunit ,Pandemic ,biology.protein ,medicine ,Animals ,Humans - Abstract
The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines.
- Published
- 2015
26. Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis.
- Author
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Lindgren, Cecilia, Tyagi, Mohit, Viljanen, Johan, Toms, Johannes, Changrong Ge, Naru Zhang, Holmdahl, Rikard, Kihlberg, Jan, and Linusson, Anna
- Published
- 2018
- Full Text
- View/download PDF
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