• KSBB Journal
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• v.25 no.6
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• pp.497-506
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• 2010

Vaccine is a protective clinical measure capable of persuading immune system against infectious agents. Vaccine can be categorized as live attenuated and inactivated. Live attenuated vaccines activate immunity similar to natural infection by replicating living organisms whereas inactivated vaccines are either whole cell vaccines, eliciting immune response by killed organisms,or subunit vaccines, stimulating immunity by non-replicating sub cellular parts. The components of vaccine play a critical role in deciding the immune response mediated by the vaccine. The innate immune responds against the antigen component. Adjuvants represent an importantcomponent of vaccine for enhancing the immunogenicity of the antigens. Subunit vaccines with isolated fractions of killed and recombinant antigens are mostly co-administered with adjuvants. The delivery system of the vaccine is another essential component to ensurethat vaccine is delivered to the right target with right dosage form. Furthermore, vaccine delivery system ensures that the desired immune response is achieved by manipulating the optimal interaction of vaccine and adjuvantwith the immune cell. The aforementioned components along with routes of administration of vaccine are the key elements of a successful vaccination procedure. Vaccines can be administered either orally or by parenteral routes. Many groups had made remarkable efforts for the development of new vaccine and delivery system. The emergence of new vaccine delivery system may lead to pursue the immunization goals with better clinical practices.

• Journal of Microbiology and Biotechnology
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• v.29 no.3
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• pp.489-499
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• 2019

Subunit vaccines are safer and more stable than live vaccines although they have the disadvantage of eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanospheres (OCNs) were used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCNs to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) was investigated. For immunization, OCNs were mixed with the two TB antigens as well as the adjuvant monophosphoryl lipid A (MPL). The protective efficacy was analyzed in vaccinated mice by aerosol Mtb challenge with a virulent strain of Mtb and the bacterial burdens were measured. The results showed that OCNs are highly effective in delivering Mtb proteins into the cytosol of BMDMs and BMDCs. Upon immunization, this vaccine formula induced robust Th1 immune response characterized by cytokine profiles from restimulated splenocytes and specific antibody titer. More importantly, enhanced cytotoxic $CD8^+$ T cell activation was observed. However, it did not reduce the bacteria burden in the lung and spleen from the aerosol Mtb challenge. Taken together, OCNs are highly effective in delivering subunit protein vaccine and induce robust Th1 and $CD8^+$ T cell response. This vaccine delivery system is suitable for application in settings where cell-mediated immune response is needed.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.370-387
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• 2023

The COVID-19 pandemic has increased demand for safe and effective vaccines. Research to develop vaccines against diseases including Middle East respiratory syndrome, Ebolavirus, human immunodeficiency virus, and various cancers would also contribute to global well-being. For successful vaccine development, the advancement of technologies such as antigen (Ag) screening, Ag delivery systems and adjuvants, and manufacturing processes is essential. Ag delivery systems are required not only to deliver a sufficient amount of Ag for vaccination, but also to enhance immune response. In addition, Ag types and their delivery systems determine the manufacturing processes of the vaccine product. Here, we analyze the characteristics of various Ag delivery systems: plasmids, viral vectors, bacterial vectors, nanoparticles, self-assembled particles, natural and artificial cells, and extracellular vesicles. This review provides insight into the current vaccine landscape and highlights promising avenues of research for the development and improvement of Ag delivery systems.

• Journal of Veterinary Science
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• v.22 no.6
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• pp.76.1-76.15
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• 2021

Background: The development of a vaccine for Jembrana disease is needed to prevent losses in Indonesia's Bali cattle industry. A DNA vaccine model (pEGFP-C1-tat) that requires a functional delivery system will be developed. Polylactic-co-glycolic acid (PLGA) may have potential as a delivery system for the vaccine model. Objectives: This study aims to evaluate the in vitro potential of PLGA as a delivery system for pEGFP-C1-tat. Methods: Consensus and codon optimization for the tat gene was completed using a bioinformatic method, and the product was inserted into a pEGFP-C1 vector. Cloning of the pEGFP-C1-tat was successfully performed, and polymerase chain reaction (PCR) and restriction analysis confirmed DNA isolation. PLGA-pEGFP-C1-tat solutions were prepared for encapsulated formulation testing, physicochemical characterization, stability testing with DNase I, and cytotoxicity testing. The PLGA-pEGFP-C1-tat solutions were transfected in HeLa cells, and gene expression was observed by fluorescent microscopy and real-time PCR. Results: The successful acquisition of transformant bacteria was confirmed by PCR. The PLGA:DNA:polyvinyl alcohol ratio formulation with optimal encapsulation was 4%:0.5%:2%, physicochemical characterization of PLGA revealed a polydispersity index value of 0.246, a particle size of 925 nm, and a zeta potential value of -2.31 mV. PLGA succeeded in protecting pEGFP-C1-tat from enzymatic degradation, and the percentage viability from the cytotoxicity test of PLGA-pEGFP-C1-tat was 98.03%. The PLGA-pEGFP-C1-tat demonstrated luminescence of the EGFP-tat fusion protein and mRNA transcription was detected. Conclusions: PLGA has good potential as a delivery system for pEGFP-C1-tat.

• KSBB Journal
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• v.26 no.6
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• pp.491-504
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• 2011

This review article provides an overview of the evolution of diphtheria vaccine, its value and its future. Diphtheria is an infectious illness caused by diphtheria toxin produced by pathogenic strains of Corynebacterium diphtheriae. It is characterized by a sore throat with membrane formation due to local tissue necrosis, which can lead to fatal airway obstruction; neural and cardiac damage are other common complications. Diphtheria vaccine was first brought to market in the 1920s, following the discovery that diphtheria toxin can be detoxified using formalin. However, conventional formalin-inactivated toxoid vaccines have some fundamental limitations. Innovative technologies and approaches with the potential to overcome these limitations are discussed in this paper. These include genetic inactivation of diphtheria toxoid, innovative vaccine delivery systems, new adjuvants (both TLR-independent and TLR-dependent adjuvants), and heat- and freeze-stable agents, as well as novel platforms for producing improved conventional vaccine, DNA vaccine, transcutaneous (microneedle-mediated) vaccine, oral vaccine and edible vaccine expressed in transgenic plants. These innovations target improvements in vaccine quality (efficacy, safety, stability and consistency), ease of use and/or thermal stability. Their successful development and use should help to increase global diphtheria vaccine coverage.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.177-183
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• 2004

Recently, studies on intranasal mucosa delivery of influenza vaccine have been actively developed because of lack of pain and ease of administration. We studied on preparation of nanoparticle delivery system using biodegradable polymer as a poly(DL-lactide-co-glycolide) (PLGA) and their binding characteristics with vaccine. Three kinds of PLGA nanoparticles were prepared by spontaneous emulsification solvent diffusion (SESD) method using sodium dodecyl sulfate and sodium laurate as an anionic surfactant and Lutrol F68 (polyethylene glycol-block-polypropylene glycol copolymer) as a nonionic surfactant. The 5-aminofluorescein labeled vaccine was coated on the surface of nanoparticles by ionic complex. The complexes between vaccine and nanoparticles were confirmed by change of the size. After vaccine coating on the surface of anionic nanoparticles, particle size was increased from 174 to 1,040 nm. However the size of nonionic nanoparticles was not more increased than size of anionic nanoparticles. The amount of coated vaccine on the surface of PLGA nanoparticles was $14.32\;{\mu}g/mg$ with sodium dodecyl sulfate, $12.41\;{\mu}g/mg$ with sodium laurate, and $9.47{\mu}g/mg$ with Lutrol F68, respectively. In conclusion, prepared nanoparticles in this study is possible to use as a virus-like nanoparticles and it could be accept in the field of influenza vaccine delivery system.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.253-258
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• 2000

In order to design the oral vaccine delivery system, we prepared the alginate micro spheres containing GFP (green fluorescent protein) as a model drug by spray method. To optimize the preparation conditions of microspheres, we investigated the effects of various parameters including nozzle pressure, nozzle opening angle, and concentrations of sodium alginate and calcium chloride. The prepared microspheres were evaluated by measuring their sizes, loading efficiency, and morphology. The particle size of microspheres was affected by the concentration of sodium alginate and calcium chloride, nozzle pressure, and nozzle opening angle. As the concentration of sodium alginate increased, GFP loading efficiency and particles size of microsphere also increased. However, it was observed to be difficult to spray the sodium alginate solution with concentration greater than 1.5% (w/v), due to high viscosity. The pressure over $3\;kgf/cm^2$ didn't affect the size of particles. As a result, the spraying method enabled us to prepare microspheres for oral vaccine delivery system. In this study, microspheres prepared with 1% (w/v) sodium alginate had greater loading efficiency and better spherical shape.

• Biotechnology and Bioprocess Engineering:BBE
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• v.4 no.1
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• pp.66-71
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• 1999

One of the practical limitations with the use of liposomes for delivery of the pharmaceutical substances such antigens is that liposomes are relatively unstable in storage. In order to extend the stability of liposome in storage without affecting their functional activity, solution-type liposomes were dehydrated to form a structurally intact dry liposomes. Comparative immunological evaluation was carried out for both dry and solution-type liposomes containing gag-V3 chimera, consequently it was found that dry liposomes elicited both humoral and cellular response as efficiently as solution-type liposemes did against the same gag-V3 antigen. Especially, long-term stability of the liposomes was remarkably enhanced by the dehydration made to loposomes without a significant change in its ability to elicit immune response in vivo. These results indicate that dry pH-sensitive liposome may become an effective delivery and adjuvant system for general vaccine development.

• Journal of Microbiology and Biotechnology
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• v.25 no.4
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• pp.526-536
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• 2015

Leptospirosis is a worldwide zoonotic disease caused by pathogenic Leptospira, a genus of which more than 250 serovars have been identified. Commercial bacterin vaccines are limited in that they lack both cross-protection against heterologous serovars and long-term protection. This study investigated in mice the immunogenicity of an anti-leptospirosis vaccine, using the outer membrane proteins LipL32 and Loa22 as antigens. The immunogenicity of this vaccine formulation was compared with those induced by vaccines based on LipL32 or Loa22 alone. A DNA-encapsulated chitosan nanoparticle was used for in vivo DNA delivery. Using a unique DNA plasmid expressing both lipL32 and loa22 for vaccination, higher antibody responses were induced than when combining plasmids harboring each gene separately. Therefore, this formulation was used to test the immunogenicity when administered by a heterologous prime (DNA)-boost (protein) immunization regimen. The specific antibody responses against LipL32 (total IgG and IgG1) and Loa22 (IgG1) were higher in mice receiving two antigens in combination than in those vaccinated with a single antigen alone. Although no significant difference in splenic CD4⁺ T cell proliferation was observed among all groups of vaccinated mice, splenocytes from mice vaccinated with two antigens exhibited higher interferon-γ and IL-2 production than when using single antigens alone upon in vitro restimulation. Taken together, the immunogenicity induced by LipL32 and Loa22 antigens in a heterologous primeboost immunization regimen using chitosan as a DNA delivery system induces higher immune response, and may be useful for developing a better vaccine for leptospirosis.

• BMB Reports
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• v.46 no.1
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• pp.17-24
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• 2013

Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy.