• Title/Summary/Keyword: therapeutic vaccine

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Statistical Consideration of Vaccine Clinical Trials (백신임상시험에 대한 통계적 고찰)

  • Nam, Ju-Sun;Kang, Seung-Ho
    • The Korean Journal of Applied Statistics
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    • v.24 no.4
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    • pp.633-646
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    • 2011
  • Clinical vaccines studies (that include cancer prevention vaccines and therapeutic vaccines) are ongoing to improve the quality of life and lengthen the human lifespan. Recently clinical trials and research on vaccines have become more active due to the prevalence of new viruses such as the A(H1N1) virus that freighted the whole word in 2009. In this paper we will describe the statistical aspects of clinical vaccine trials and outline the current situation of domestic and international vaccine development.

Fusion Peptide Improves Stability and Bioactivity of Single Chain Antibody against Rabies Virus

  • Xi, Hualong;Zhang, Kaixin;Yin, Yanchun;Gu, Tiejun;Sun, Qing;Shi, Linqing;Zhang, Renxia;Jiang, Chunlai;Kong, Wei;Wu, Yongge
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.718-724
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    • 2017
  • The combination of rabies immunoglobulin (RIG) with a vaccine is currently effective against rabies infections, but improvements are needed. Genetic engineering antibody technology is an attractive approach for developing novel antibodies to replace RIG. In our previous study, a single-chain variable fragment, scFv57R, against rabies virus glycoprotein was constructed. However, its inherent weak stability and short half-life compared with the parent RIG may limit its diagnostic and therapeutic application. Therefore, an acidic tail of synuclein (ATS) derived from the C-terminal acidic tail of human alpha-synuclein protein was fused to the C-terminus of scFv57R in order to help it resist adverse stress and improve the stability and half-life. The tail showed no apparent effect on the preparation procedure and affinity of the protein, nor did it change the neutralizing potency in vitro. In the ELISA test of molecular stability, the ATS fusion form of the protein, scFv57R-ATS, showed an increase in thermal stability and longer half-life in serum than scFv57R. The protection against fatal rabies virus challenge improved after fusing the tail to the scFv, which may be attributed to the improved stability. Thus, the ATS fusion approach presented here is easily implemented and can be used as a new strategy to improve the stability and half-life of engineered antibody proteins for practical applications.

Pathogenesis, Dianosis, and Prophylactic Vaccine Development for Foot-and-Mouth Disease (구제역의 병리기전 및 진단, 예방백신 개발)

  • Moon, Sun-Hwa;Yang, Joo-Sung
    • Applied Biological Chemistry
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    • v.48 no.4
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    • pp.301-310
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    • 2005
  • Foot-and-mouth disease (FMD) is a highly contagious disease of mammals and has a great potential for causing severe economic loss in susceptible cloven-hoofed animals, such as cattle, pigs, sheep, goats and buffalo. FMDV, a member of the Aphthovirus genus in the Picornaviridae family, is a non-enveloped icosahedral virus that contains a positive sense RNA of about 8.2 kb in size. The genome carries one open reading frame consisting of 3 regions: capsid protein coding region P1, replication related protein coding region P2, and RNA-dependent RNA polymerase coding region P3. FMDV infects pharynx epithelial cell in the respiratory tract and viral replication is active in lung epithelial cell. Morbidity is extremely high. A FMD outbreak in Korea in 2002 caused severe economic loss. Although intense research is undergoing to develop appropriate drugs to treat FMDV infection, there is no specific therapeutic for controlling FMDV infection. Moreover, there is an increasing demand for the development of vaccine strategies against FMDV infection in many countries. In this report, more effective prevention strategies against FMDV infection were reviewed.

Noroviruses: Recent Updates

  • Chung, Ju-Young
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.15 no.1
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    • pp.1-7
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    • 2012
  • Noroviruses (NoVs) are one major etiologic agent in acute gastroenteritis (AGE) in all ages and are the primary cause of food-borne gastroenteritis worldwide. GII-4 NoVs has predominated since 1990s, and novel recombinant strains have been reported worldwide. Researchers face difficulties in making vaccines and therapeutic agents against NoVs due to the lack of cell culture and animal-model systems and the rapid emergence of novel variant strains. Recently, a randomized clinical trial for intranasal NoVs vaccine has been reported, which casts a light in the way of vaccine production. This review discusses the recent findings on the structure, immunity, and vaccination of NoVs.

The Necessity of Vaccine Education for Pharmacists and Development of a Vaccine Leaflet for Patient Counseling (약사의 백신에 대한 교육의 필요성 및 환자 상담을 위한 소책자 개발)

  • Kim, Mi-Kyung;Kim, Hyun-Ah;Cho, Eun;Lee, Ok-Sang;Lim, Sung-Cil
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.3
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    • pp.280-291
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    • 2011
  • Vaccines are products for immunization which can provoke antibodies by eliciting immune reponses without causing disease and have played an important role in preventing fatal and contagious diseases as well as H1N1 influenza. They are classified by two following categories; lived attenuated vaccine and killed vaccine and currently commonly using vaccines are BCG, diphtheria, tetanus, mumps, measles, rubella, polio, Haemophilus influenza type b, hepatitis B, influenza etc. All vaccines must be used correctly to reach optimal therapeutic goals and also informed well to patients to decrease potential problems. In order to do, pharmacists must have good knowledge of vaccines. The purpose of this study is to evaluate the necessity of vaccine education for pharmacists and develop a vaccine leaflet for patient counseling. We have performed a survey with questionnaire for a total of 176 pharmacists and nurses(hospital pharmacists, n=65; community pharmacists, n=50; hospital nurses, n=61) from January 27th to March 12th, 2010. The questionnaire includes items about vaccine education and counseling and 12 quizzes to evaluate responders' knowledge of vaccines. We used the SPSS(Version 12. for windows) program to analyze the data. In results, 94.9% of all responders said they had not been educated on vaccines. And only 1.1% of all responders said they know about vaccines enough to counsel patients. Pharmacists who have an experience recommending vaccines to other people are 21.7%. On the other hand, nurses who have an experience recommending vaccines to other people are 55.7%(p=0.000). The mean number of correct answers at the 12 quizzes are followings; hospital pharmacist, 8.1; community pharmacist, 6.1, hospital nurses, 6.2(p=0.000). A vaccine leaflet for patient counseling is developed with several references. In conclusion, due to no opportunity of vaccine education, pharmacists have no confidence to counsel patients and lack of knowledge of vaccine. But importance of vaccine's role is increasing, pharmacists should counsel patients in vaccination. So they need vaccine education and a vaccine leaflet will be helpful for their counseling.

Prophylactic and Therapeutic Applications of Genetic Materials Carrying Viral Apoptotic Function

  • Yang Joo-Sung
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2002.10a
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    • pp.118-120
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    • 2002
  • Genetic materials including DNA plasmid are effective delivery vehicle to express interesting gene efficiently and safely not to generate replication competent virus. Moreover, it has advantages to design a better vector and to simplify manufacturing and storage condition. To understand a possible pathogenic mechanism by a flavivirus, West Nile virus (WNV), WNV genome sequence was aligned to other pathogenic viral genome. Interestingly, WNV capsid (Cp) amino acid sequence has some homology to HIV-l Vpr protein. These proteins induce apoptosis in human cell lines as well as in vivo and cell cycle arrest. Therefore, DNA plasmid carrying apoptosis-inducing and cell cycle arresting viral proteins including a HIV-1 Vpr and a WNV Cp protein can be useful for anti-cancer therapeutic applications. This WNV Cp protein is an early expressed protein which can be a reasonable target antigen (Ag) for vaccine design. Immunization of a DNA construct encoding WNV Cp protein induces a strong Ag-specific humoral and Th1-type immune responses in animal. Therefore, DNA plasmid encoding apoptotic viral proteins can be useful tool for therapeutic and prophylactic applications.

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Nanovesicles: Diagnostic and Therapeutic Tools in Nanoscale Medicine

  • Kim, Minji;Kim, Moonjeong;Kim, Kwang-sun
    • Applied Science and Convergence Technology
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    • v.25 no.6
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    • pp.103-107
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    • 2016
  • The use of nanovesicles (NVs) has contributed to nanotechnology in the development of new concept medicine to compete with diseases of deleterious and infectious to human health. Due to their properties of size, morphology, and biocompatibility NVs have great impact on public health especially in the development of new therapeutic and prophylaxis approaches in addition to the device for biosensors to diagnose human diseases. Recent data also strongly suggest that NVs are regarded as innovative materials in developing for vaccines and diagnostic tools. In this review, we focus on the basic concepts and recent applications of NVs to utilize or engineer them as therapeutic materials.

A Novel Mutant of Human Papillomavirus Type 18 E6E7 Fusion Gene and its Transforming Activity

  • Zhou, Zhi-Xiang;Zhao, Chen;Li, Qian-Qian;Zeng, Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7395-7399
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    • 2014
  • Background: Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this study, the optimized fusion gene HPV18 E6E7 (HPV18 ofE6E7) was constructed according to genetic codon usage for human genes. At the same time, for safety future clinical application, a mutant of HPV18 ofE6E7 fusion gene was generated by site-directed mutagenesis at L52G for the E6 protein and C98G for the E7 protein. Results: HPV18-E6E7 mutant (HPV18 ofmE6E7) constructed in this work not only lost the transformation capability for NIH 3T3 cells and tumorigenicity in BALB/c nude mice, but also maintained very good stability and antigenicity. Conclusion: These results suggest that the mutant should undergo further study for application as a safe antigenspecific therapeutic vaccine for HPV18-associated tumors.

Immunotherapeutic Effects of Dendritic Cells Pulsed with a Coden-optimized HPV 16 E6 and E7 Fusion Gene in Vivo and in Vitro

  • Zhou, Zhi-Xiang;Li, Dan;Guan, Shan-Shan;Zhao, Chen;Li, Ze-Lin;Zeng, Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3843-3847
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    • 2015
  • Background: Cervical cancer is the second most common cause of cancer related death of women. Persistent HPV infection, especially with high-risk types such as HPV16 and HPV18, has been identified to be the primary cause of cervical cancer. E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed exclusively in HPV infected tissues, and thereby represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this work, we used recombinant adenovirus expressing coden-optimized HPV16 E6 and E7 fusion protein (Ad-ofE6E7) to prime dendritic cells (DC-ofE6E7), to investigate the ability of primed DC vaccine in eliciting antitumor immunity in vitro and vivo. Results: Our results indicated that DC-ofE6E7 vaccine co-culturing with splenocytes could strongly induce a tumor-specific cytotoxic T lymphocyte (CTL) response and kill the TC-1 cells effectively in vitro. Moreover, DC-ofE6E7 vaccine induced protective immunity against the challenge of TC-1 cancer cells in vivo. Conclusions: The results suggested that the HPV16 ofE6E7 primed DC vaccine has potential application for cervical cancer immunotherapy.

Cell-Based IL-15:IL-15Rα Secreting Vaccine as an Effective Therapy for CT26 Colon Cancer in Mice

  • Thi, Van Anh Do;Jeon, Hyung Min;Park, Sang Min;Lee, Hayyoung;Kim, Young Sang
    • Molecules and Cells
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    • v.42 no.12
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    • pp.869-883
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    • 2019
  • Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4+ T, CD8+ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.