• Biomolecules & Therapeutics
• /
• v.26 no.3
• /
• pp.242-254
• /
• 2018

Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express ${\alpha}$- and ${\beta}$-defensins, which are known for their antiviral and antibacterial activities. This review describes the application of human defensins. We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents. Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons. Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models. Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the 'defensin vaccine' concept to prime the body with a controlled supply of human defensins. In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.

• Journal of Plant Biotechnology
• /
• v.32 no.4
• /
• pp.233-241
• /
• 2005

Plants have considerable advantages for the production of antigenic proteins because they provide an inexpensive source of protein and an easy administration of vaccine. Since a publication describing edible plant vaccine of HBsAg in 1992, a number of laboratories around the world have studied the use of plants as the bioreactor to produce antigenic proteins of human or animal pathogens. Over the last ten years, these works have been mainly focused on three major strategies for the production of antigenic proteins in plants: stable genetic transformation of either the nuclear or plastid genome, or transient expression in plants using viral vectors. As many antigenic proteins have been expressed in tobacco, also several laboratories have succeeded to express genes encoding antigenic proteins in other crop plants: potato, tomato, maize, carrot, soybean and spinach. At present many works for the production of edible plant vaccine against bacteria-mediated diseases have mostly performed the studies of enterotoxins and adhesion proteins. Also the development of new-type antigens (pili, flagella, surface protein, other enterotoxin and exotoxin etc.) is required for various targets and more efficacy to immunize against microorganism pathogens. Many works mostly studied in experimental animals had good results, and phase I clinical trial of LTB clearly indicated its immunogenic ability. On the other hand, edible plant vaccines have still problems remained to be solved. In addition to the accumulation of sufficient antigen in plants, human health, environment and agriculture regulation should be proven. Also oral tolerance, the physiological response to food antigens and commensal flora is the induction of a state of specific immunological unresponsiveness, needs to be addressed before plant-derived vaccine becomes a therapeutic option.

• Journal of fish pathology
• /
• v.27 no.1
• /
• pp.47-56
• /
• 2014

Propolis is a beehive product with a very complex chemical composition, widely used in folk medicine because of its several therapeutic activities. This study was conducted to measure the efficacy of propolis on non-specific defense reactions, specific immune response, and protection levels against pathogen challenge with Streptococcus iniae. in vitro and in vivo. In vitro, the phagocytic activity and NBT assay of peripheral blood leukocytes (PBL) were evaluated in a various propolis extractsconcentrations (0, 10, 50, 100, 150, 250 and $500{\mu}g/ml$). The optimal concentration showing activation of propolis extracts was determined to $100{\mu}g/ml$. In vivo, they were divided into four groups (PBS, propoli extractss, vaccine, propolis extracts + vaccine) in vivo. Fish were received i.p. injection of either PBS or propolis extracts, and in the presence or absence of formalin inactivated S. iniae ($1{\times}10^8$ CFU/fish), respectively. The level of haematocrit is not affected among experimental groups. The phagocytic activity and the NBT reduction activities of head kidney phagocyte were markedly (p<0.05)augmented in the propolis extracts groups than in the PBS-control group, respectively. The level of serum lysozyme activity was significantly (p<0.05) increased in the propolis extracts treated groups than in the PBS-control group. The agglutinin titer was significantly (p<0.05) enhanced in the vaccine+propolis extracts group than in the vaccine group, but there was no difference between PBS-control and propolis treated group. The results of the present study suggest that propolis extracts seems to be a promising compounds of non-specific immune stimulator, also being able to use a good adjuvant.

• Microbiology and Biotechnology Letters
• /
• v.50 no.3
• /
• pp.430-435
• /
• 2022

The infectious bursal disease (IBD) is a highly contagious and acute poultry disease caused by Birnavirus. However, the vaccination is the only disease prevention, but several factors impeded vaccine development. Thus, a need for time to develop a novel technique for managing and treating respiratory diseases in poultry birds. Passive immunization is a hope and a possible alternative used in birds to meet this need. The current research attempted to produce egg yolk-based polyclonal antibodies against the IBD virus. The benefits of IgY include ease of extraction, lack of reaction with mammalian Fc receptors, and low production cost. Commercial layers were immunized with inactivated IBD virus subcutaneously according to the treatment regimen. The eggs were gathered daily, and yolk antibodies were extracted with the ammonium sulfate precipitation technique. The use of an indirect hemagglutination test demonstrated that IgY was IBD-specific. Until the end of the experiment, the specific IgY immunoglobulins did not lose activity when stored at 4℃. The specific immunoglobulin (IgY) treated challenged birds were demonstrated 92% recovery in comparison to the control group. The study implies that the IBDV specific IgY is an easily prepared and rich source of antibodies and offers an alternative therapeutic agent to cure IBD-infected birds.

• IMMUNE NETWORK
• /
• v.20 no.3
• /
• pp.23.1-23.20
• /
• 2020

Sepsis is conceptually defined as life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Although there has been significant advancement in recent decades in defining and understanding sepsis pathology, clinical management of sepsis is challenging due to difficulties in diagnosis, a lack of reliable prognostic biomarkers, and treatment options that are largely limited to antibiotic therapy and fundamental supportive measures. The lack of reliable diagnostic and prognostic tests makes it difficult to triage patients who are in need of more urgent care. Furthermore, while the acute inpatient treatment of sepsis warrants ongoing attention and investigation, efforts must also be directed toward longer term survival and outcomes. Sepsis survivors experience incomplete recovery, with long-term health impairments that may require both cognitive and physical treatment and rehabilitation. This review summarizes recent advances in sepsis prognosis research and discusses progress made in elucidating the underlying causes of prolonged health deficits experienced by patients surviving the early phases of sepsis.

• IMMUNE NETWORK
• /
• v.12 no.6
• /
• pp.269-276
• /
• 2012

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either $CD34^+$ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-${\beta}$ secretion were higher in SDC but CCR7 expression, IFN-${\gamma}$ and IL-10 secretion were higher in MoDC. The proportion of $CD11c^+CD8a^+$ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-${\gamma}$ secreting $CD8^+$ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.3109-3116
• /
• 2013

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

• Korean Journal of Clinical Laboratory Science
• /
• v.54 no.1
• /
• pp.38-48
• /
• 2022

Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.9
• /
• pp.1444-1452
• /
• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

• IMMUNE NETWORK
• /
• v.3 no.3
• /
• pp.188-200
• /
• 2003

Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.