RESUMEN

Chronic infectious diseases refer to diseases that require a long period of time from onset to cure or death, the use of therapeutic vaccines has recently emerged to eradicate diseases. Currently, clinical research is underway to develop therapeutic vaccines for chronic infectious diseases based on various vaccine formulations, and the recent success of the messenger RNA vaccine platform and efforts to apply it to therapeutic vaccines are having a positive impact on conquering chronic infectious diseases. However, since research on the development of therapeutic vaccines is still relatively lacking compared to prophylactic vaccines, there is a need to focus more on the development of therapeutic vaccines to overcome threats to human health caused by chronic infectious diseases. In order to accelerate the development of therapeutic vaccines for chronic infectious diseases in the future, it is necessary to establish a clear concept of therapeutic vaccines suitable for the characteristics of each chronic infectious disease, as well as standardize vaccine effectiveness evaluation methods, secure standards/reference materials, and simplify the vaccine approval procedure.

RESUMEN

The current production of the Japanese encephalitis virus (JEV) vaccine is based on animal cells, where various risk factors for human health should be resolved. This study used a transient expression system to express the chimeric protein composed of antigenic epitopes from the JEV envelope (E) protein in Nicotiana benthamiana. JEV multi-epitope peptide (MEP) sequences fused with FLAG-tag or 6× His-tag at the C- or N-terminus for the purification were introduced into plant expression vectors and used for transient expression. Among the constructs, vector pSK480, which expresses MEP fused with a FLAG-tag at the C-terminus, showed the highest level of expression and yield in purification. Optimization of transient expression procedures further improved the target protein yield. The purified MEP protein was applied to an ICR mouse and successfully induced an antibody against JEV, which demonstrates the potential of the plant-produced JEV MEP as an alternative vaccine candidate.

Asunto(s)

RESUMEN

Coronavirus disease 2019 (Covid-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) became a pandemic, causing significant burden on public health worldwide. Although the timely development and production of mRNA and adenoviral vector vaccines against SARS-CoV-2 have been successful, issues still exist in vaccine platforms for wide use and production. With the potential for proliferative capability and heat stability, the Newcastle disease virus (NDV)-vectored vaccine is a highly economical and conceivable candidate for treating emerging diseases. In this study, a recombinant NDV-vectored vaccine expressing the spike (S) protein of SARS-CoV-2, rK148/beta-S, was developed and evaluated for its efficacy against SARS-CoV-2 in K18-hACE-2 transgenic mice. Intramuscular vaccination with low dose (106.0 EID50) conferred a survival rate of 76 % after lethal challenge of a SARS-CoV-2 beta (B.1.351) variant. When administered with a high dose (107.0 EID50), vaccinated mice exhibited 100 % survival rate and reduced lung viral load against both beta and delta variants (B.1.617.2). Together with the protective immunity, rK148/beta-S is an accessible and cost-effective SARS-CoV-2 vaccine.

Asunto(s)

RESUMEN

For the development of biodegradable superabsorbent polymers, the effect of the cross-linking length on the absorption characteristics of the Na salt of polyaspartic acid (PAspNa) was demonstrated using different concentrations of diamine cross-linking agents bearing carbon chains of different lengths, viz., ethylenediamine, 1,6-hexamethylenediamine, 1,8-diaminooctane, 1,10-diaminodecane, and 1,12-diaminododecane were used as cross-linking agents. The absorption of PAspNa was measured in deionised water and in a 0.9% aqueous NaCl solution. Under the conditions tested, when the alkyl chain of PAspNa was too short or too long, the absorbency was low and the cross-linking length was optimum. The success of the cross-linking reaction was confirmed by FT-IR spectroscopy. The degree of cross-linking was estimated and the ideal concentration for maximum water absorption was determined by elemental analysis. The sample obtained by cross-linking 1,8-diaminooctane at a concentration of 0.11 g/g polysuccinimide (PSI) showed the highest absorption. The thermal properties of each material were determined by dynamic scanning calorimetry. Therefore, the length of the cross-linking agent was found to strongly influence water absorption.

RESUMEN

Globally, infection by seasonal influenza viruses causes 3-5 million cases of severe illness and 290,000-650,000 respiratory deaths each year. Various influenza vaccines, including inactivated split- and subunit-type, recombinant and live attenuated vaccines, have been developed since the 1930s when it was discovered that influenza viruses could be cultivated in embryonated eggs. However, the protection rate offered by these vaccines is rather low, especially in very young children and the elderly. In this review, we describe the history of influenza vaccine development, the immune responses induced by the vaccines and the adjuvants applied. Further, we suggest future directions for improving the effectiveness of influenza vaccines in all age groups. This includes the development of an influenza vaccine that induces a balanced T helper cell type 1 and type 2 immune responses based on the understanding of the immune system, and the development of a broad-spectrum influenza vaccine that can increase effectiveness despite antigen shifts and drifts, which are characteristics of the influenza virus. A brighter future can be envisaged if the development of an adjuvant that is safe and effective is realized.

Asunto(s)

RESUMEN

The complete genome sequence of a new polerovirus found naturally infecting Artemisia princeps, artemisia virus B (ArtVB), was determined using high-throughput sequencing. The ArtVB genome comprises 6,141 nucleotides and contains six putative open reading frames (ORF0 to ORF5) with a genome structure typical of poleroviruses. A multiple sequence alignment showed that the complete ArtVB genome shares 50.98% nucleotide sequence identity with ixeridium yellow mottle virus 1 (IxYMaV-1, GenBank accession no. KT868949). ArtVB shares the highest amino acid sequence identity in P0 and P3-P5 (21.54%-51.69%) with other known poleroviruses. Phylogenetic analysis indicated that ArtVB should be considered a member of a new species within the genus Polerovirus, family Luteoviridae.

Asunto(s)

RESUMEN

Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment.

Asunto(s)

RESUMEN

In order to develop a successful vaccine against deadly diseases with a wide range of antigenic diversity, an in-depth knowledge of the molecules and signaling mechanisms between the vaccine candidates and immune cells is required. Therefore, monitoring vaccine components, such as antigen or adjuvants, and immune cell dynamics at the vaccination site or draining lymph nodes can provide important information to understand more about the vaccine response. This review briefly introduces and describes various non-invasive molecular imaging methods for visualizing immune cell dynamics after vaccination.

RESUMEN

Vaccination is one of the most successful strategies to prevent diseases caused by pathogens. Although various expression systems including Escherichia coli, yeast, insect, and mammalian cells are currently used for producing many of vaccines, these conventional platforms have the limitation of post-translational modification, high cost, and expensive scalability. In this respect, the plant-based expression system has been considered as an attractive platform to produce recombinant vaccines due to fast, cost-effective and scalable production as well as safety. This review discusses the development of plant-derived vaccines and the current stage of plant-based expression system.

RESUMEN

Vaccination is one of the most successful strategies to prevent diseases caused by pathogens. Although various expression systems including Escherichia coli, yeast, insect, and mammalian cells are currently used for producing many of vaccines, these conventional platforms have the limitation of post-translational modification, high cost, and expensive scalability. In this respect, the plant-based expression system has been considered as an attractive platform to produce recombinant vaccines due to fast, cost-effective and scalable production as well as safety. This review discusses the development of plant-derived vaccines and the current stage of plant-based expression system.

Asunto(s)

RESUMEN

In order to develop a successful vaccine against deadly diseases with a wide range of antigenic diversity, an in-depth knowledge of the molecules and signaling mechanisms between the vaccine candidates and immune cells is required. Therefore, monitoring vaccine components, such as antigen or adjuvants, and immune cell dynamics at the vaccination site or draining lymph nodes can provide important information to understand more about the vaccine response. This review briefly introduces and describes various non-invasive molecular imaging methods for visualizing immune cell dynamics after vaccination.

Asunto(s)

RESUMEN

PURPOSE: Study on the pathogen and the pathogen-related disease require the information at both cellular and organism level. However, lack of appropriate high-quality antibodies and the difference between the experimental animal models make it difficult to analyze in vivo mechanism of pathogen-related diseases. For more reliable research on the infection and immune-response of pathogen-related diseases, accurate analysis is essential to provide spatiotemporal information of pathogens and immune activity to avoid false-positive or mis-interpretations. In this regards, we have developed a method for tracking Francisella tularensis in the animal model without using the specific antibodies for the F. tularensis. MATERIALS AND METHODS: A dual reporter plasmid using GFP-Lux with putative bacterioferritin promoter (pBfr) was constructed and transformed to F. tularensis live vaccine strain to generate F. tularensis LVS (FtLVS)-GFP-Lux for both fluorescence and bioluminescence imaging. For vaccination to F. tularensis infection, FtLVS and lipopolysaccharide (LPS) from FtLVS were used. RESULTS: We visualized the bacterial replication of F. tularensis in the cells using fluorescence and bioluminescence imaging, and traced the spatio-temporal process of F. tularensis pathogenesis in mice. Vaccination with LPS purified from FtLVS greatly reduced the bacterial replication of FtLVS in animal model, and the effect of vaccination was also successfully monitored with in vivo imaging. CONCLUSION: We successfully established dual reporter labeled F. tularensis for cellular and whole body imaging. Our simple and integrated imaging analysis system would provide useful information for in vivo analysis of F. tularensis infection as well as in vitro experiments, which have not been fully explained yet with various technical problems.

RESUMEN

Organoid is an in vitro multicellular form mimicking in vivo organ. Its similarity to human organ including cellular organization, molecular expression patterns, as well as genetic signatures enables to study the characteristics of infectious agents and host-pathogen interaction. For the features of organoid, this system also can be potentially used to cultivate currently uncultivable viruses of vaccine candidates. This paper will briefly describe problems in the current culture system for virus production and the possibility of organoid as culture system for viral vaccine and their current limitations that should be solved to meet the goal.

RESUMEN

Organoid is an in vitro multicellular form mimicking in vivo organ. Its similarity to human organ including cellular organization, molecular expression patterns, as well as genetic signatures enables to study the characteristics of infectious agents and host-pathogen interaction. For the features of organoid, this system also can be potentially used to cultivate currently uncultivable viruses of vaccine candidates. This paper will briefly describe problems in the current culture system for virus production and the possibility of organoid as culture system for viral vaccine and their current limitations that should be solved to meet the goal.

Asunto(s)

RESUMEN

PURPOSE: Study on the pathogen and the pathogen-related disease require the information at both cellular and organism level. However, lack of appropriate high-quality antibodies and the difference between the experimental animal models make it difficult to analyze in vivo mechanism of pathogen-related diseases. For more reliable research on the infection and immune-response of pathogen-related diseases, accurate analysis is essential to provide spatiotemporal information of pathogens and immune activity to avoid false-positive or mis-interpretations. In this regards, we have developed a method for tracking Francisella tularensis in the animal model without using the specific antibodies for the F. tularensis. MATERIALS AND METHODS: A dual reporter plasmid using GFP-Lux with putative bacterioferritin promoter (pBfr) was constructed and transformed to F. tularensis live vaccine strain to generate F. tularensis LVS (FtLVS)-GFP-Lux for both fluorescence and bioluminescence imaging. For vaccination to F. tularensis infection, FtLVS and lipopolysaccharide (LPS) from FtLVS were used. RESULTS: We visualized the bacterial replication of F. tularensis in the cells using fluorescence and bioluminescence imaging, and traced the spatio-temporal process of F. tularensis pathogenesis in mice. Vaccination with LPS purified from FtLVS greatly reduced the bacterial replication of FtLVS in animal model, and the effect of vaccination was also successfully monitored with in vivo imaging. CONCLUSION: We successfully established dual reporter labeled F. tularensis for cellular and whole body imaging. Our simple and integrated imaging analysis system would provide useful information for in vivo analysis of F. tularensis infection as well as in vitro experiments, which have not been fully explained yet with various technical problems.

Asunto(s)

RESUMEN

Assessing antigen concentration of vaccine is essential step in determining the quality of the vaccine prior to vaccination. After vaccination, vaccine-induced antibody titer should also be measured to verify the vaccine efficacy. Since conventional assay used for vaccine concentrations and induced Ab-titers is antibody-based enzyme-linked immunosorbent assay, the assay inevitably brings drawbacks of antibody such as high cost for production, limited stability, and inconsistent quality between lot-to-lots. Aptamer is single-stranded nucleic acid having three-dimensional structure and has features overcoming limitations of antibody. This review will briefly introduce the features of aptamer and potential of aptamer-based system for evaluation of vaccine efficacy.

RESUMEN

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.

RESUMEN

Assessing antigen concentration of vaccine is essential step in determining the quality of the vaccine prior to vaccination. After vaccination, vaccine-induced antibody titer should also be measured to verify the vaccine efficacy. Since conventional assay used for vaccine concentrations and induced Ab-titers is antibody-based enzyme-linked immunosorbent assay, the assay inevitably brings drawbacks of antibody such as high cost for production, limited stability, and inconsistent quality between lot-to-lots. Aptamer is single-stranded nucleic acid having three-dimensional structure and has features overcoming limitations of antibody. This review will briefly introduce the features of aptamer and potential of aptamer-based system for evaluation of vaccine efficacy.

Asunto(s)

RESUMEN

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.

Asunto(s)