Purpose: Immunization with Porphyromonas gingivalis heat shock protein 60 (PgHSP60) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSP60 peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. Methods: Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSP60-derived peptide 14 (Pep14) or peptide 19 (Pep19), or a Western diet and immunization with Pep14 or Pep19 before challenge with Pep14 or Pep19. Results: Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pep14 nasal immunization than in mice that received a Western diet and no Pep14 immunization with or without Pep14 challenge. An immunoblot profile failed to detect serum reactivity to Pep14 in any of the study groups. Stimulation by either Pep14 or Pep19 strongly promoted the induction of CD4+CD25+ forkhead box P3 (FoxP3)+ human regulatory T cells (Tregs) in vitro. However, the expression of mouse splenic CD4+CD25+FoxP3+ Tregs was lower in the Pep14-immunized mice than in the Pep14-challenged or Pep19-immunized mice. Levels of serum interferon gamma (IFN-γ) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pep14-immunized mice than in the other groups. Induction of CD25- IL-17+ T helper 17 (Th17) cells was attenuated in the Pep14-immunized mice. Conclusions: Nasal immunization with Pep14 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-γ and/or suppressing Th17-mediated immunity.
Fayoumi chicks were vaccinated with fowl pox virus vaccine and pigeon pox virus vaccine. The protective potentiality of the two vaccines was compared in field condition in Bangladesh. The percentage of 'take reaction' was assessed to conclude its relationship with better immune response and recorded 93.33% and 100% in birds of group B and group C, respectively. The mean passive hemagglutination (PHA) antibody titre after primary vaccination was $32{\pm}14.81$ in group B and $33{\pm}13.66$ in group C. Following booster vaccination, the mean PHA titres level at pre challenge of group B was $46.93{\pm}16.52\;and\;55.46{\pm}14.64$ in group C. The PHA titre of group B and C at two weeks post challenge recorded $93.86{\pm}33.04\;and\;110.93{\pm}29.29$, respectively. PHA titre significantly (P<0.01) increased after vaccination and post challenge compared to pre- vaccination titre. There was significant variation (p<0.01) of PHA titre at pre challenge in these groups using different vaccine combinations, but all the vaccinated birds resisted challenge infection.
Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.
Retroviruses genes have been inserted into the human genome for millions of years. These retroviruses are now inactive due to mutations such as deletions or nonsense mutations. After mutation, retroviruses eventually became fixed in the genome in their endogenous forms and existed as traces of ancient viruses. These retroviruses are called endogenous retroviruses (ERVs), with the human form known as human endogenous retrovirus. HERV cannot become a fully active virus, but a number of viral proteins or even virus particles are expressed under various conditions. Compared to endogenous retroviruses, some exogenous retroviruses are still infectious and can threaten human life. Among these, human immunodeficiency virus (HIV) is one of the most well-known and best-studied. Recent studies have shown some elements of HERV were activated by HIV infection and interact with HIV-derived proteins. In addition, many studies have attempted to use HERV as vaccination against HIV infection. This review will describe the regulation and interaction between HERV and HIV infection and mention the development of vaccines and therapeutic agents against HIV infection by using HERV elements.
Cancer/testis (CT) antigens are immunogenic in cancer patients, exhibit highly tissue-restricted expression, and are considered promising target molecules for cancer vaccines. We investigated the expression of 13 CT genes in 29 Korean patients with primary breast carcinoma. The most frequently expressed CT genes were MAGE-3 (66%) and MAGE-1 (57%), followed by LAGE-1 (55%), NY-SAR-35 (49%), MAGE-4 (41%), NY-ESO-1 (38%), CT-7 (24%) and SSX-4 (24%), whereas SSX-1, SSX-2, MAGE-10 and NY-TLU-57 were found to be expressed significantly less often (3-7%) and SCP-l not all. Expression of at least one antigen was observed in 28 breast cancer samples. Immunohistochemistry was performed for NY-ESO-l and MAGE-3 protein expression in breast tumor samples. NY-ESO-l and MAGE-3 proteins were expressed in 11 of 29 (38%) and 12 of 29 (41 %) breast tumors. Our results suggest that CT antigens may be potential candidates for polyvalent immunotherapy in Korean breast cancer patients.
Tuberculosis is the leading infectious disease in the world. It is urgent to develop new vaccine and treating drugs. Besides vaccines, we want to know the effects of regular swim training on TB infection in the mouse model. This study was designed to examine the effects of regular swim training on lung and spleen TB counts and $INF-\gamma$ activity in the trained mice at different temperature. The trained mice underwent a 10-wk endurance swim training (5 times/wk) in water at $29\~33^{\circ}C$ (WWG) and $21\~23^{\circ}C$(CWG) for 60 min. And they were divided into 3 groups according to the regular swim training (CG; control, WWG; warm water group, and CWG; cold water group). Mice were challenged by aerosol infection with M. tuberculosis H37Rv using an inhalation device (Glas-Col, Terre Haute, Ind.) calibrated to deliver bacteria into lungs. Three weeks after immunization, the mice were challenged. Four weeks after challenge, the mice were sacrificed and the numbers of viable bacteria in lung and spleen were determined by plating serial dilution of whole organ homogenates on nutrient Middlebrook 7H11 agar (Difco, Detroit, MI). Colonies were counted after four weeks incubation at $37^{\circ}C$. All data were expressed as mean, standard deviation by using SPSS package program (win 10.0). The result through the statistical analysis of this data were summarized as follows; In the weight changes, there were significant differences among CG, WWG, and CWG following the swim training at different temperature, and CWG was the lowest. In the change of $INF-\gamma$ following the swim training, there were significant differences (p<.05) among CG, WWG, and CWG after stimulated with media and CFP. In MTB counts, there were significant differences (p<.05) between CG and WWG in the lung. And also there were significant differences (p<.05) among CG, WWG, and CWG. These results suggest that regular swim training suppress Th1 immune response caused by decreased $INF-\gamma$ level in the WWG, Also For the WWG, highly increased level of TB counts appear in the lung and spleen compare to CG.
Classical swine fever virus (CSFV) is the etiologic agent of classical swine fever, a highly contagious disease that causes significant economic losses to the swine industry. The lapinized C-strain, a widely used vaccine strain against CSFV, has low growth efficiency in cell culture, which limits the productivity in the vaccine industry. In this study, a recombinant virus derived from C-strain was constructed and subjected to continuous passaging in PK-15 cells with the goal of acquiring a high progeny virus yield. A cell-adapted virus variant, RecCpp80, had nearly 1,000-fold higher titer than its parent C-strain but lost the ability to induce fever in rabbits. Sequence analysis of cell-adapted RecC variants indicated that at least six nucleotide changes were fixed in RecCpp80. Further adaption of RecCpp80 variant in swine testicle cells led to a higher virus yield without additional mutations. Introduction of each of these residues into the wild-type RecC backbone showed that one mutation, M979R (T3310G), located in the C-terminal region of E2 might be closely related to the cell-adapted phenotype. Rabbit inoculation revealed that $RecCpp40_{+10}$ failed to induce fever in rabbits, whereas $RecCpp80_{+10}$ caused a fever response similar to the commercial C-strain vaccine. In conclusion, the C-strain can be adapted to cell culture by introducing specific mutations in its E2 protein. The mutations in RecCpp80 that led to the loss of fever response in rabbits require further investigation. Continuous passaging of the C-strain-based recombinant viruses in PK-15 cells could enhance its in vitro adaption. The non-synonymous mutations at 3310 and 3531 might play major roles in the enhanced capacity of general virus reproduction. Such findings may help design a modified C-strain for improved productivity of commercial vaccines at reduced production cost.
Kim, Do-Soon;Park, Jung-Eun;Cho, Hyun-Wook;Joo, Woo-Hong;Yee, Sung-Tae
Journal of Life Science
/
v.17
no.3
s.83
/
pp.427-434
/
2007
Dendritic cells (DCs) play a pivotal roles in the initiation of T cell-mediated immune responses, making them an attractive in immuno vaccines. Angelica gigas and Cnidium officinale were a medicinal herb widely used in Asian countries. In this study, we examined the effects of A. gigas and C. officinale extracts on the DCs functional maturation and phono-type. Immature DCs were cultured in the presence of GM-CSF and IL-4, and the generated immature DCs were stimulated with OVA in the presence or absence A. gigas and C. officinale extracts, respectively, for 24 hours. The antigen-presenting capacity of A. gigas and C. officinale extracts-treated DCs as analyzed by $CD4^+$ helper T cell clone (OVA-specific) proliferation and cytokines (IL-2 and $IFN-{\gamma}$) production were significantly increased. But A. gigas and C. officinale extracts were not directly effected $CD4^+$ helper T cell clone function. Also, the expression of surface co-stimulatory molecules, including major histocompatibility complex (MHC) class II, CD86 and CD11c, is increased on DCs that were stimulated with A. gigas and C. officinale extracts. These results indicate the immunomodulatory properties of A. gigas and C. officinale extracts, which might be medical supplies or health foods.
Kim Se-Heon;Choi Eun-Chang;Kim Han-Su;Chang Jung-Hyun;Kim Ji-Hoon;Kim Kwang-Moon
Korean Journal of Head & Neck Oncology
/
v.19
no.1
/
pp.25-33
/
2003
Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.
This study was undertaken to investigate the distribution of human papillomavirus (HPV) subtypes and cervical lesions in Busan. Furthermore, the cytological and histological findings of cervical lesions were compared to determine the usefulness of the currently released vaccines. HPV subtypes of 2,130 patients who visited Haeundae Paik Hospital between January 2013 and March 2016 were analyzed by the HPV 9G DNA chip. Liquid-based cytological examination was performed, and subtypes were classified according to the 2001 guidelines of The Bethesda System. Biopsy or hysterectomy specimens were subjected to hematoxylin and eosin staining for histological examinations. Of the total 2,130 cases, 1,254 (58.9%) were positive for HPV, and 876 (41.1%) were negative. Of these, 152 (7.1%), 97 (4.6%) and 80 (3.8%) were identified as HPV 16, 68 and 56, respectively. Of the 329 cases encompassing the above three HPV subtypes, histopathological analysis diagnosed 155 (47.1%) cases with CIN2 or higher grade. Notably, the occurrences of HPV subtypes 16, 68, 56, 58 and 51 were most frequently diagnosed in Busan. Further analysis revealed that administration of GardasilⓇ 9, the currently available vaccine in the market, exerts no protection against subtypes 68, 59 and 51. This study aims to provide an important reference for future HPV vaccination programs in Busan.
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