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Poultry Science Jun 2023An immunization experiment was conducted in specific pathogen-free chickens with the inactivated Newcastle disease virus (NDV) vaccine encapsulated in the...
An immunization experiment was conducted in specific pathogen-free chickens with the inactivated Newcastle disease virus (NDV) vaccine encapsulated in the poly-(lactic-co-glycolic) acid (PLGA) nanoparticles (NP) to evaluate its immunogenicity and protective efficacy. The NDV vaccine was prepared by inactivating one virulent Indian strain of NDV belonging to Genotype VII by using beta-propiolactone. PLGA nanoparticles encapsulating inactivated NDV were prepared by the solvent evaporation method. Scanning electron microscopy and zeta sizer analysis revealed that the (PLGA+NDV) NP were spherical, with an average size of 300 nm, having a zeta potential of -6 mV. The encapsulation efficiency and loading efficiency were 72% and 2.4%, respectively. On immunization trial in chicken, the (PLGA+NDV) NP induced significantly (P < 0.0001) higher levels of HI and IgY antibodies with the peak HI titer of 2 and higher expression of IL-4 mRNA. The consistency of higher antibody levels suggests slow and pulsatile release of the antigens from the (PLGA+NDV) NP. The nano-NDV vaccine also induced cell mediated immunity with higher expression of IFN-γ indicating strong Th1 mediated immune responses in contrast to the commercial oil adjuvanted inactivated NDV vaccine. Further, the (PLGA+NDV) NP afforded 100% protection against the virulent NDV challenge. Our results suggested that PLGA NP have adjuvant potential on induction of humoral as well as Th1 biased cell mediated immune responses and also enhanced protective efficacy of the inactivated NDV vaccine. This study provides an insight for development of PLGA NP based inactivated NDV vaccine using the same genotype circulating in the field as well as for other avian diseases at exigencies.
Topics: Animals; Newcastle disease virus; Newcastle Disease; Chickens; Vaccines, Inactivated; Glycols; Adjuvants, Immunologic; Immunity, Cellular; Nanoparticles; Viral Vaccines
PubMed: 37116285
DOI: 10.1016/j.psj.2023.102679 -
Nature Medicine Jun 2012Safe and effective vaccines are crucial for maintaining public health and reducing the global burden of infectious disease. Here we introduce a new vaccine platform that...
Safe and effective vaccines are crucial for maintaining public health and reducing the global burden of infectious disease. Here we introduce a new vaccine platform that uses hydrogen peroxide (H(2)O(2)) to inactivate viruses for vaccine production. H(2)O(2) rapidly inactivates both RNA and DNA viruses with minimal damage to antigenic structure or immunogenicity and is a highly effective method when compared with conventional vaccine inactivation approaches such as formaldehyde or β-propiolactone. Mice immunized with H(2)O(2)-inactivated lymphocytic choriomeningitis virus (LCMV) generated cytolytic, multifunctional virus-specific CD8(+) T cells that conferred protection against chronic LCMV infection. Likewise, mice vaccinated with H(2)O(2)-inactivated vaccinia virus or H(2)O(2)-inactivated West Nile virus showed high virus-specific neutralizing antibody titers and were fully protected against lethal challenge. Together, these studies demonstrate that H(2)O(2)-based vaccines are highly immunogenic, provide protection against a range of viral pathogens in mice and represent a promising new approach to future vaccine development.
Topics: Adult; Animals; Antibodies, Neutralizing; Antibodies, Viral; CD8-Positive T-Lymphocytes; Female; Humans; Hydrogen Peroxide; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Middle Aged; Vaccination; Vaccines, Inactivated; Viral Vaccines; West Nile Fever; West Nile virus
PubMed: 22635006
DOI: 10.1038/nm.2763 -
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 -
Applied Microbiology Feb 1970Four strains of influenza virus were treated with Formalin, Merthiolate, Merthiolate and Formalin, ultraviolet light, and beta-propiolactone (BPL) for 18, 48, and 72 hr....
Effect of formalin, beta-propiolactone, merthiolate, and ultraviolet light upon influenza virus infectivity chicken cell agglutination, hemagglutination, and antigenicity.
Four strains of influenza virus were treated with Formalin, Merthiolate, Merthiolate and Formalin, ultraviolet light, and beta-propiolactone (BPL) for 18, 48, and 72 hr. Infectivity, chicken cell agglutination (CCA), hemagglutination (HA), and antigenicity determinations were made. Except for Merthiolate, each method of inactivation was equally effective in reducing infectivity. Loss of infectivity was related to length of treatment. CCA determinations were higher for all treated groups except for BPL-treated samples; these had lower determinations. BPL treatment also lowered the HA titer. Antigenicity was lessened by BPL treatment and by Merthiolate and Formalin treatment. Generally, the length of inactivation up to 72 hr did not affect CCA, HA, or antigenicity determinations. For the most part, there was no significant differences in the reactivity of the four strains.
Topics: Agglutination; Agglutination Tests; Animals; Antigen-Antibody Reactions; Antiviral Agents; Chick Embryo; Formaldehyde; Hemagglutination Inhibition Tests; Hemagglutination, Viral; Hemagglutinins, Viral; Heterocyclic Compounds; Lactones; Mercury; Organometallic Compounds; Orthomyxoviridae; Rabbits; Radiation Effects; Ultraviolet Rays
PubMed: 5437304
DOI: 10.1128/am.19.2.290-294.1970 -
Journal of Tissue Engineering and... Jan 2008Biodegradable and biocompatible polymeric scaffolds have been recently introduced for tissue regeneration purpose. In the present study we aimed to develop...
Biodegradable and biocompatible polymeric scaffolds have been recently introduced for tissue regeneration purpose. In the present study we aimed to develop polymeric-based scaffolds for bone regeneration. Two polyesters, poly-beta-propiolactone (PBPL), poly-epsilon-caprolactone (PCPL) and two polyfumarates, polydiisopropyl fumarate (PDIPF), polydicyclohexyl fumarate (PDCF) were chosen to prepare films which can support osteoblastic growth. Scanning electron microscopy and water contact angle were used to characterize the matrices. Biodegradation studies were performed both in PBS buffer and using an in vitro macrophage degradation assay. Mouse calvaria-derived MC3T3E1 cells and UMR106 rat osteosarcoma cell lines were used to perform biocompatibility and cytotoxicity studies. The polyesters, the most hydrophilic polymers studied, showed a rougher and more porous surfaces than the polyfumarates. Under acellular conditions, only PBPL was degraded by hydrolytic mechanisms. However, macrophages performed an active degradation of all polymeric films. Osteoblasts developed well-defined actin fibres without evidence of cytotoxicity when growing on the films. The number of UMR106 osteoblasts that adhered to the PBPL-based film was higher than that of the cells attached to the PECL and polyfumarates (PDIPF and PDCF) matrices. Both UMR106 and MC3T3E1 osteoblastic lines showed protein levels comparable to control conditions, demonstrating that they grew well on all surfaces. However, UMR106 cells showed a significant increase in proliferation on polyester-derived scaffolds (PBPL and PECL). The alkaline phosphatase activity of UMR106, an osteoblastic marker, was significantly higher than that of control plastic dishes. MC3T3E1 cells expressed similar levels of this differentiation marker in all polymeric matrices. We found similar collagen protein content after 48 h culture of UMR106 cells on all surfaces. However, important differences were evident in the MC3T3E1 line. In conclusion, the synthetic polymeric-based scaffold we have developed and studied supports adhesion, growth and differentiation of two osteoblastic cell lines, suggesting that they could be useful in bone tissue regeneration.
Topics: Animals; Biocompatible Materials; Bone and Bones; Cell Adhesion; Cell Differentiation; Cell Line; Cell Shape; Chemical Phenomena; Chemistry, Physical; Fumarates; Mice; Microscopy, Electron, Scanning; Molecular Structure; Osteoblasts; Polyesters; Polymers; Rats; Tissue Engineering; Water
PubMed: 18273918
DOI: 10.1002/term.62 -
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 -
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 -
Journal of Virology Apr 2017The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both...
The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received recombinant rabies viruses carrying only the CDV attachment protein according to the same immunization scheme died. Irrespective of the CDV antigens used, all animals developed protective titers against rabies virus, illustrating that a bivalent rabies virus-based vaccine against CDV induces protective immune responses against both pathogens.
Topics: Animals; Antibodies, Viral; Disease Models, Animal; Distemper; Distemper Virus, Canine; Ferrets; Rabies virus; Survival Analysis; Vaccines, Inactivated; Vaccines, Synthetic; Viral Vaccines
PubMed: 28148801
DOI: 10.1128/JVI.02077-16 -
Biologicals : Journal of the... Sep 2010Cell culture-based production methods may assist in meeting increasing demand for seasonal influenza vaccines and developing production flexibility required for...
Cell culture-based production methods may assist in meeting increasing demand for seasonal influenza vaccines and developing production flexibility required for addressing influenza pandemics. MDCK-33016PF cells are used in propagation of a cell-based seasonal influenza vaccine (Optaflu); but, like most continuous cell lines, can grow in immunocompromised mice to produce tumors. It is, therefore, essential that no residual cells remain within the vaccine, that cell lysates or DNA are not oncogenic, and that the cell substrate does not contain oncogenic viruses or oncogenic DNA. Multiple, redundant processes ensure the safety of influenza vaccines produced in MDCK-33016PF cells. The probability of a residual cell being present in a dose of vaccine is approximately 1 in 10(34). Residual MDCK-DNA is < or =10 ng per dose and the ss-propiolactone used to inactivate influenza virus results in reduction of detectable DNA to less than 200 base pairs (bp). Degenerate PCR and specific PCR confirm exclusion of oncogenic viruses. The manufacturing process has been validated for its capacity to remove and inactivate viruses. We conclude that the theoretical risks arising from manufacturing seasonal influenza vaccine using MDCK-33016PF cells are reduced to levels that are effectively zero by the multiple, orthogonal processes used during production.
Topics: Algorithms; Animals; Animals, Newborn; Cell Extracts; Cell Fractionation; Cell Transformation, Viral; Cells, Cultured; Cricetinae; DNA; Dogs; Female; Humans; Influenza Vaccines; Kidney; Male; Mice; Mice, Nude; Rats; Virus Activation
PubMed: 20537553
DOI: 10.1016/j.biologicals.2010.04.003