• Journal of Fisheries and Marine Sciences Education
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• v.27 no.5
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• pp.1470-1478
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• 2015

Adjuvant is an immune enhancer commonly used during vaccination to enhance the host immune response. In the present study, we produced the several recombinant protein from immune related gene of olive flounder (Paralichthys olivaceus). Especially, to produce the soluble type of recombinant protein, we constructed the MBP (Maltose binding protein) fusion G-CSF (Granulocyte colony stimulating factor) recombinant protein among the flounder immune related genes. To verify the immune stimulatory effect and safety of this recombinant protein (rPoGCSF), expression changes of several immune genes were tested using quantitative real-time PCR method with gene specific primer from flounder head kidney leukocytes. As a result, we confirmed that the rPoGCSF has an ability of immune stimulatory effect, also it has broad range of pH and temperature.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.7
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• pp.1044-1051
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• 2016

The present study compared the differential functions of two groups of adjuvants, Montanide incomplete Seppic adjuvant (ISA) series and Quil A, cholesterol, dimethyl dioctadecyl ammonium bromide, and Carbopol (QCDC) formulations, in chicken by analyzing published microarray data associated with each type of vaccine adjuvants. In the biological function analysis for differentially expressed genes altered by two different adjuvant groups, ISA series and QCDC formulations showed differential effects when chickens were immunized with a recombinant immunogenic protein of Eimeria. Among the biological functions, six categories were modified in both adjuvant types. However, with respect to "Response to stimulus", no biological process was modified by the two adjuvant groups at the same time. The QCDC adjuvants showed effects on the biological processes (BPs) including the innate immune response and the immune response to the external stimulus such as toxin and bacterium, while the ISA adjuvants modified the BPs to regulate cell movement and the response to stress. In pathway analysis, ISA adjuvants altered the genes involved in the functions related with cell junctions and the elimination of exogenous and endogenous macromolecules. The analysis in the present study could contribute to the development of precise adjuvants based on molecular signatures related with their immunological functions.

• Tuberculosis and Respiratory Diseases
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• v.87 no.1
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• pp.31-39
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• 2024

After the successful development of targeted therapy and immunotherapy for the treatment of advanced-stage non-small cell lung cancer (NSCLC), these innovative treatment options are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermal growth factor receptor-mutated tumors and atezolizumab and pembrolizumab for selected patients with resectable NSCLC. Numerous studies on various targeted therapies and immunotherapy with or without chemotherapy are currently ongoing in the adjuvant setting. However, several questions regarding optimal strategies for adjuvant treatment remain unanswered. The present review summarizes the available literature, focusing on recent advances and ongoing trials with targeted therapy and immunotherapy in the adjuvant treatment of early-stage NSCLC.

• IMMUNE NETWORK
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• v.10 no.6
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• pp.198-205
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• 2010

Background: A crucial limitation of DNA vaccines is its weak immunogenicity, especially in terms of eliciting antibody responses in non-human primates or humans; therefore, it is essential to enhance immune responses to vaccination for the development of successful DNA vaccines for humans. Methods: Here, we approached this issue by evaluating interleukin-7 (IL-7) as a genetic adjuvant in cynomolgus monkeys immunized with multigenic HCV DNA vaccine. Results: Codelivery of human IL-7 (hIL-7)-encoding DNA appeared to increase DNA vaccine-induced antibody responses specific for HCV E2 protein, which plays a critical role in protecting from HCV infection. HCV-specific T cell responses were also significantly enhanced by codelivery of hIL-7 DNA. Interestingly, the augmentation of T cell responses by codelivery of hIL-7 DNA was shown to be due to the enhancement of both the breadth and magnitude of immune responses against dominant and subdominant epitopes. Conclusion: Taken together, these findings suggest that the hIL-7-expressing plasmid serves as a promising vaccine adjuvant capable of eliciting enhanced vaccine-induced antibody and broad T cell responses.

• Journal of Gastric Cancer
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• v.19 no.3
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• pp.235-253
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• 2019

Gastric cancer (GC) is one of the deadliest malignancies in the world. Currently, clinical treatment decisions are mostly made based on the extent of the tumor and its anatomy, such as tumor-node-metastasis staging. Recent advances in genome-wide molecular technology have enabled delineation of the molecular characteristics of GC. Based on this, efforts have been made to classify GC into molecular subtypes with distinct prognosis and therapeutic response. Simplified algorithms based on protein and RNA expressions have been proposed to reproduce the GC classification in the clinical field. Furthermore, a recent study established a single patient classifier (SPC) predicting the prognosis and chemotherapy response of resectable GC patients based on a 4-gene real-time polymerase chain reaction assay. GC patient stratification according to SPC will enable personalized therapeutic strategies in adjuvant settings. At the same time, patient-derived xenografts and patient-derived organoids are now emerging as novel preclinical models for the treatment of GC. These models recapitulate the complex features of the primary tumor, which is expected to facilitate both drug development and clinical therapeutic decision making. An integrated approach applying molecular patient stratification and patient-derived models in the clinical realm is considered a turning point in precision medicine in GC.

• IMMUNE NETWORK
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• v.7 no.4
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• pp.186-196
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• 2007

Background: Although IL-12 has been widely accepted to playa central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. Methods: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly ($A_{DL}$-lactic-co-glycolic acid) (PLGA). Results: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific $CD4^+\;and\;CD8^+$ T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of $CD8^+$ T cell response was not detectable when $CD4^+$ T cell knockout mice were subjected to vaccination, indicating that the enhancement of the $CD8^+$ T cell response by IL-12EM is dependent on $CD4^+$ T cell "help". Conclusion: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.

• Journal of Microbiology and Biotechnology
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• v.27 no.11
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• pp.2060-2069
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• 2017

Newcastle disease is a serious infectious disease in the poultry industry. The commercial vaccines can only offer limited protection and some of them are expensive and need adjuvants. At present, DNA vaccines are widely used. However, the immune responses induced by DNA vaccines are too slow and low. Here, we constructed the transfer vectors with a different number of C3d as molecular adjuvants (n = 1, 2, 4, or 6), and the vectors were cloned into the optimal eukaryotic expression plasmid (pVAXI-optiF) that expressed the F gene of Newcastle disease virus (NDV), and named pVAXI-F(o)-C3d1, pVAXI -F(o)-C3d2, pVAXI-F(o)-C3d4, and pVAXI-F(o)-C3d6, respectively. Cell transfection test indicated that pVAXI-F(o)-C3d6 showed the highest expression. In vivo immunization showed that the chickens immunized with pVAXI-F(o)-C3d6 intramuscularly induced better immune responses than the chickens immunized with the other plasmids. The protective efficacy of pVAXI-F(o)-C3d6 was 80% after challenge with the highly virulent NDV strain F48E9. The results in this study showed that C3d6 could be used as a molecular adjuvant to quickly induce an effective immune response to control NDV.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.41.1-41.16
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• 2022

The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

• BMB Reports
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• v.50 no.10
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• pp.496-503
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• 2017

The human body loses several billions of cells daily. When cells die in vivo, the corpse of each dead cell is immediately cleared. Specifically, dead cells are efficiently recognized and cleared by multiple types of neighboring phagocytes. Early research on cell death focused more on molecular mechanisms of cell death regulation while the cellular corpses were merely considered cellular debris. However, it has come to light that various biological stimuli following cell death are important for immune regulation. Clearance of normal dead cells occurs silently in immune tolerance. Exogenous or mutated antigens of malignant or infected cells can initiate adaptive immunity, thereby inducing immunogenicity by adjuvant signals. Several pathogens and cancer cells have strategies to limit the adjuvant signals and escape immune surveillance. In this review, we present an overview of the mechanisms of dead cell clearance and its immune regulations.

• Journal of Marine Life Science
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• v.4 no.1
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• pp.1-13
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• 2019

Fucoidan is a physiologically functional ingredient extracted from seaweed brown algae, which is a sulfated polysaccharide containing fucose as a main molecule backbone. Fucoidan has a variety of immune-modulating or -stimulating effects, including promoting antigen uptake and enhancing anti-bacterial, anti-viral and anti-tumor effects. In addition, recent studies have suggested the possibility of use of fucoidan as a vaccine adjuvant in the field of human vaccine. Use of fucoidan as supplementary feeds have already been studied, but the development of fucoidan as an adjuvant of fish vaccine is still premature. However, the intracellular uptake of fucoidan differs depending on the molecular weight of fucoidan, and there is a limit to the study on specific immune response including the production of antibodies to fish caused by an artificial infection of pathogen. Although the safety of fucoidan has been demonstrated in animal cells, there is a need to confirm the safety of fucoidan in fish. Therefore, active research in this field is needed to use fucoidan as a vaccine adjuvant. This study discussed the effects of fucoidan on immune stimulation, humoraland cellular- immunity including humans and animals. The prospect of fucoidan as a vaccine adjuvant in fisheries also reviewed.