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Food and Environmental Virology Mar 2020Influenza A virus (IAV) infection is perennially one of the leading causes of death worldwide. Effective therapy and vaccination are needed to control viral expansion....
Influenza A virus (IAV) infection is perennially one of the leading causes of death worldwide. Effective therapy and vaccination are needed to control viral expansion. However, current anti-IAV drugs risk inducing drug-resistant virus emergence. Although intranasal administration of whole inactivated virus vaccine can induce efficient protective immunity, formalin and β-propiolactone are the currently used and harmful inactivating agents. Here, we analyzed the antiviral activity of hibiscus (Hibiscus sabdariffa L.) tea extract against human IAV and evaluated its potential as a novel anti-IAV drug and a safe inactivating agent for whole inactivated vaccine. The in vitro study revealed that the pH of hibiscus tea extract is acidic, and its rapid and potent antiviral activity relied largely on the acidic pH. Furthermore, the mouse study showed that the acidic extract was not effective for either therapeutic or vaccination purposes. However, hibiscus tea extract and protocatechuic acid, one of the major components of the extract, showed not only potent acid-dependent antiviral activity but also weak low-pH-independent activity. The low-pH-independent activity did not affect the conformation of immunodominant hemagglutinin protein. Although this low-pH-independent activity is very limited, it may be suitable for the application to medication and vaccination because this activity is not affected by the neutral blood environment and does not lose antigenicity of hemagglutinin. Further study of the low-pH-independent antiviral mechanism and attempts to enhance the antiviral activity may establish a novel anti-IAV therapy and vaccination strategy.
Topics: Animals; Antiviral Agents; Female; Hibiscus; Humans; Hydrogen-Ion Concentration; Influenza A virus; Influenza, Human; Mice; Mice, Inbred BALB C; Plant Extracts
PubMed: 31620998
DOI: 10.1007/s12560-019-09408-x -
Physical Chemistry Chemical Physics :... May 2023To explain the polarization Raman noncoincidence effect of specific polar bonds and the noncoincidence phenomenon between FT-Raman and FT-IR spectra, aggregation-induced...
To explain the polarization Raman noncoincidence effect of specific polar bonds and the noncoincidence phenomenon between FT-Raman and FT-IR spectra, aggregation-induced spectral splitting theory was proposed. In this paper, the vibration splitting theory was demonstrated using two strategies: improving the spectral resolution with cryogenic matrix isolation techniques and identifying cases where the coupling splitting is large enough to be distinguishable. The monomer and dimer splitting bands of acetone were detected when cryogenically isolated by the Ar matrix. Additionally, the polarization Raman and two-dimensional infrared spectra of a β-propiolactone (PIL)/CCl binary mixture were collected at room temperature, and the spectral splitting phenomenon was clearly observed. The dynamic transformation between the monomer and dimer could be achieved and detected by adjusting the PIL concentration. The observed splitting phenomenon was further confirmed by theoretical DFT calculations based on the monomer and dimer of PIL, as well as the FT-IR and FT-Raman spectra of PIL. Concentration-triggered 2D-COS synchronous and asynchronous spectra also confirmed the splitting phenomenon and the dilution kinetics of PIL/CCl.
PubMed: 37194330
DOI: 10.1039/d3cp01391j -
Structure (London, England : 1993) Nov 2020The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made...
The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized β-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses.
Topics: Animals; Betacoronavirus; COVID-19 Vaccines; Chlorocebus aethiops; Coronavirus Infections; Cryoelectron Microscopy; Disinfectants; Electron Microscope Tomography; Humans; Propiolactone; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccines, Inactivated; Vero Cells; Viral Vaccines; Virion
PubMed: 33058760
DOI: 10.1016/j.str.2020.10.001 -
Viruses Jan 2018In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in...
In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR) suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, β-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines.
Topics: Animals; Animals, Newborn; Antibodies, Neutralizing; Cell Line, Tumor; Disease Models, Animal; Enterovirus D, Human; Enterovirus Infections; Female; Humans; Immunity, Maternally-Acquired; Mice; Mice, Inbred ICR; Neutralization Tests; Vaccines, Inactivated; Viral Load; Viral Tropism; Viral Vaccines
PubMed: 29385753
DOI: 10.3390/v10020058 -
Emerging Microbes & Infections Dec 2021The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines...
The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo- and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the vaccine manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Callithrix; Cricetinae; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Guinea Pigs; Humans; Immunity, Humoral; Immunogenicity, Vaccine; Immunoglobulin G; Male; Mesocricetus; Mice; Mice, Inbred BALB C; Rats; Rats, Wistar; SARS-CoV-2; Time Factors; Vaccines, Inactivated
PubMed: 34427172
DOI: 10.1080/22221751.2021.1971569 -
Fish & Shellfish Immunology Feb 2016Herpesviral haematopoietic necrosis (HVHN) of gibel carp (Carassius gibelio) is a newly emerged infectious disease caused by cyprinid herpesvirus 2 (CyHV-2) and has...
Herpesviral haematopoietic necrosis (HVHN) of gibel carp (Carassius gibelio) is a newly emerged infectious disease caused by cyprinid herpesvirus 2 (CyHV-2) and has caused huge economic losses in aquaculture operations. Currently, no effective methods are available for the control of the disease. In this study, β-propiolactone inactivated cyprinid herpesvirus 2 (CyHV-2) vaccine was prepared, and the immune response and protection in cultured gibel carp after vaccination was thoroughly investigated. This included blood cell counting and classification, phagocytic activity, lysozyme and superoxide dismutase activity, neutralizing antibody titration, immune gene expression analysis, and determination of the relative percent survival in vaccinated gibel carp. The results of blood cell counts indicated that the numbers of the red and white blood cells in the peripheral blood of immunized gibel carp increased significantly at day 4 and day 7 after vaccination (p < 0.01). The differential leukocyte count of neutrophils and monocytes were significantly different compared to the control group at day 4 and 7 and the percentage of lymphocytes reached a peak at day 21. The phagocytic percentage and phagocytic index peaked at day 4 post-vaccination. The lysozyme activity and superoxide dismutase activity were significantly increased compared to the control group (p < 0.01). The serum neutralizing antibody titer peaked (203.03 ± 13.44) at day 21. The qPCR analysis revealed that the expression of the immune genes interlukin 11 and complement component C3 were significantly up-regulated in the immunized group. The challenge test demonstrated that the immunized group had a relative survival rate of 71.4%. These results indicate that the inactivated CyHV-2 vaccine induced both non-specific and specific anti-viral immune responses that resulted in significant protection against HVHN disease and mortality in gibel carp.
Topics: Animals; Cyprinidae; DNA Virus Infections; DNA Viruses; Fish Diseases; Immunity, Humoral; Immunity, Innate; Propiolactone; Vaccines, Inactivated; Viral Vaccines
PubMed: 26772479
DOI: 10.1016/j.fsi.2016.01.003 -
IScience Feb 2023Vaccines have relieved the public health burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and globally inactivated vaccines are most widely used....
Vaccines have relieved the public health burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and globally inactivated vaccines are most widely used. However, poor vaccination accessibility and waning immunity maintain the pandemic, driving emergence of variants. We developed an inactivated SARS-CoV-2 (I-SARS-CoV-2) vaccine based on a viral isolate with the Spike mutation D614G, produced in Vero cells in a scalable bioreactor, inactivated with β-propiolactone, purified by membrane-based steric exclusion chromatography, and adjuvanted with MF59-like adjuvant AddaVax. I-SARS-CoV-2 and a derived split vaccine induced persisting neutralizing antibodies in mice; moreover, lyophilized antigen was immunogenic. Following homologous challenge, I-SARS-CoV-2 immunized hamsters were protected against disease and lung pathology. In contrast with reports for widely used vaccines, hamster plasma similarly neutralized the homologous and the Delta (B.1.617.2) variant viruses, whereas the Omicron (B.1.1.529) variant was neutralized less efficiently. Applied bioprocessing approaches offer advantages regarding scalability and production, potentially benefitting worldwide vaccine coverage.
PubMed: 36644321
DOI: 10.1016/j.isci.2023.105949 -
Nanomaterials (Basel, Switzerland) May 2019Zwitterionic polymers are suitable for replacing poly(ethylene glycol) (PEG) polymers because of their better antifouling properties, but zwitterionic polymers have poor...
Zwitterionic polymers are suitable for replacing poly(ethylene glycol) (PEG) polymers because of their better antifouling properties, but zwitterionic polymers have poor mechanical properties, strong water absorption, and their homopolymers should not be used directly. To solve these problems, a reversible-addition fragmentation chain transfer (RAFT) polymerization process was used to prepare copolymers comprised of zwitterionic side chains that were attached to an ITO glass substrate using spin-casting. The presence of 4-vinylpyridine (4VP) and zwitterion chains on these polymer-coated ITO surfaces was confirmed using 1H NMR, FTIR, and GPC analyses, with successful surface functionalization confirmed using water contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) studies. Changes in water contact angles and C/O ratios (XPS) analysis demonstrated that the functionalization of these polymers with β-propiolactone resulted in hydrophilic mixed 4VP/zwitterionic polymers. Protein adsorption and cell attachment assays were used to optimize the ratio of the zwitterionic component to maximize the antifouling properties of the polymer brush surface. This work demonstrated that the antifouling surface coatings could be readily prepared using a "P4VP-modified" method, that is, the functionality of P4VP to modify the prepared zwitterionic polymer. We believe these materials are likely to be useful for the preparation of biomaterials for biosensing and diagnostic applications.
PubMed: 31067668
DOI: 10.3390/nano9050706 -
Vaccine Apr 2015Chicken anemia virus (CAV) is an immunosuppressive virus that causes chicken infectious anemia (CIA) which is a highly contagious avian disease. CAV causes major...
BACKGROUND
Chicken anemia virus (CAV) is an immunosuppressive virus that causes chicken infectious anemia (CIA) which is a highly contagious avian disease. CAV causes major economic losses in the poultry industry worldwide. The current CAV vaccine is a live attenuated strain administered in the drinking water that risks horizontal infection of other chickens. The purpose of this study was to develop a novel vaccine against CAV that can be administered safely using a highly pathogenic isolate inactivated with β-propiolactone hydrolysis that would protect chicks from CAV.
METHODS
Hens were vaccinated twice intramuscularly with a novel CAV GD-G-12 inactivated vaccine and the humoral immune responses of the hens and offspring were monitored by ELISA. A heterologous intramuscular challenge using the CAV strain GD-E-12 was conducted in the chicks hatched from vaccinated or unvaccinated hens.
RESULTS
The vaccine strain, GD-G-12, was shown to be highly pathogenic prior to inactivation evidenced by thymic atrophy and bleeding, and weight loss. The inactivated vaccine was considered safe and showed no signs of pathogenicity. High titers of CAV specific antibodies were detected in the vaccinated hens and in their chicks, indicating vertical transfer of maternal antibodies. Furthermore, the chicks hatched from vaccinated hens were resistant to a heterologous CAV challenge and showed no signs of weight loss and thymic atrophy and bleeding.
CONCLUSION
Our studies are proof of principle that inactivated GD-G-12 might be a novel vaccine candidate to prevent CAV infection, and highlight the utility of using an inactivated virus for this vaccine.
Topics: Animals; Antibodies, Viral; Chicken anemia virus; Chickens; Circoviridae Infections; Poultry Diseases; Thymus Gland; Vaccines, Inactivated; Viral Vaccines
PubMed: 25758933
DOI: 10.1016/j.vaccine.2015.02.066 -
Development of an Antigen Detection Kit Capable of Discriminating the Omicron Mutants of SARS-CoV-2.Vaccines Jan 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world, caused millions of deaths and a severe illness which poses a serious threat to...
INTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world, caused millions of deaths and a severe illness which poses a serious threat to human health.
OBJECTIVE
To develop an antigen detection kit that can identify Omicron novel coronavirus mutants.
METHODS
BALB/c mice were immunized with the nucleocapsid protein of SARS-CoV-2 Omicron mutant treated with β-propiolactone. After fusion of myeloma cells with immune cells, Elisa was used to screen the cell lines capable of producing monoclonal antibodies. The detection kit was prepared by colloidal gold immunochromatography. Finally, the sensitivity, specificity and anti-interference of the kit were evaluated by simulating positive samples.
RESULTS
The sensitivity of the SARS-CoV-2 antigen detection kit can reach 62.5 TCID/mL, and it has good inclusiveness for different SARS-CoV-2 strains. The kit had no cross-reaction with common respiratory pathogens, and its sensitivity was still not affected under the action of different concentrations of interferences, indicating that it had good specificity and stability.
CONCLUSION
In this study, monoclonal antibodies with high specificity to the N protein of the Omicron mutant strain were obtained by monoclonal antibody screening technology. Colloidal gold immunochromatography technology was used to prepare an antigen detection kit with high sensitivity to detect and identify the mutant Omicron strain.
PubMed: 36851181
DOI: 10.3390/vaccines11020303