• Title/Summary/Keyword: DNA vaccines

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DNA Vaccines against Infectious Diseases and Cancer

  • Han, Duk-Jae;Weiner, David B.;Sin, Jeong-Im
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.1-15
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    • 2010
  • Progress in the development of DNA vaccines and their delivery strategies has been made since their initial concept as a next generation vaccine. Since DNA vaccine includes non-infectious DNA parts of pathogens, it can't cause disease yet it closely mimic the natural process of infection and immune responses. Despite their early promising results of controlling infectious diseases and cancer in small animal models, DNA vaccines failed to display a level of immunogenicity required for combating these diseases in humans, possibly due to their lower protein expression levels. However, increasing evidence has shown that DNA vaccines are clinically well-tolerated and safe. Furthermore, one notable advantage of DNA vaccines includes convenient utilities of plasmid DNAs coding for antigens. For instance, any emerging pathogens could be prevented easily and timely by allowing the simple exchange of antigen-encoding genes. In this review, newly developed DNA vaccine strategies, including electroporation, which has emerged as a potent method for DNA delivery, targeting infectious diseases and cancer will be discussed with a focus on any on-going DNA vaccine trials or progress made pre-clinically and in clinics.

Cancer Vaccines (암백신)

  • Son, Eun-Wha;In, Sang-Whan;Pyo, Suhk-Neung
    • IMMUNE NETWORK
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    • v.5 no.2
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    • pp.55-67
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    • 2005
  • Cancer vaccine is an active immunotherapy to stimulate the immune system to mount a response against the tumor specific antigen. Working as a stimulant to the body's own immune system, cancer vaccines help the body recognize and destroy targeted cancers and may help to shrink advanced tumors. Research is currently underway to develop therapeutic cancer vaccines. It is also possible to develop prophylactic vaccines in the future. The whole cell approach to eradicate cancer has used whole cancer cells to make vaccine. In an early stage of this approach, whole cell lysate or a mixture of immunoadjuvant and inactivated cancer cells has been used. Improved vaccines are being developed that utilize cytokines or costimulatory molecules to mount an attack against cancer cells. In case of melanoma, these vaccines are expected to have a therapeutic effect of vaccine. Furthermore, it is attempting to treat stomach cancer, colorectal cancer, pancreatic cancer, and prostate cancer. Other vaccines are being developing that are peptide vaccine, recombinant vaccine and dendritic cell vaccine. Out of them, reintroduction of antigen-specific dendritic cells into patient and DNA vaccine are mostly being conducted. Currently, research and development efforts are underway to develop therapeutic cancer vaccine such as DNA vaccine for the treatment of multiple forms of cancers.

A Study of Immunogenicity and Reactogenicity of Hepatitis B Vaccine Made by Recombinant DNA Techniques in Yeast (효모재조합 DNA B형 간염백신의 면역효과에 관한 연구)

  • Min, Chang-Hong;Kim, Kyo-Myung;Lee, Kyu-Man
    • The Journal of the Korean Society for Microbiology
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    • v.21 no.2
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    • pp.243-249
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    • 1986
  • A study of the immunogenicity and reactogenicity of two doses of lot H(10, 20 mcg), two doses of lot L (20, 40 mcg) of the Smith Kline-RIT recombinant DNA yeast-derived hepatitis B vaccine and a 20-mcg dose of the Merck Sharp and Dohme plasma-derived hepatitis B vaccine was conducted in young adults under randomized, double-blind conditions. Immunization was carried out according to a 0-, 1-, and 6-month vaccination schedule. Results indicated that the yeast-derived hepatitis B vaccine was well tolerated and immunogenic. Reactogenicity to both yeast- and plasma-derived vaccines was mild in severity and low in incidence with no significant differences appearing between the study groups. One month after the third dose, the yeast-derived vaccines induced a high degree of soroconversion ranging between 95.0% and 100%. The response was not lot or dose-dependent. The administration of the plasma-derived vaccine resulted in anti-HBs geometric mean titres statistically signifirantly higher than those elicited by the different yeast-derived hepatitis B vaccines one month after the third dose of vaccine but the difference was not large enough to be of great clinical significance.

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Perspectives of AIDS Vaccine Development: T Cell-based Vaccine

  • Sung, Young Chul
    • IMMUNE NETWORK
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    • v.2 no.1
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    • pp.1-5
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    • 2002
  • Estimated number of adults and children newly infected with HIV-1 during 2001 alone is 5 million in total. An effective vaccine, in addition to education & public health approaches, has been believed to be the best option to stop the HIV-1 transmission, especially for developing countries. Among AIDS vaccine candidates, DNA vaccine is relatively safe and, in a certain extent, mimics some attributes of live attenuated vaccine, with regard to in vivo gene expression & the type of immunity induced. We recently demonstrated that DNA vaccines expressing SIVmac239 structural and regulatory genes, augmented with coadministration of IL-12 mutant induced the strongest T cell responses, resulting in low to undetectable setpoint viral loads, stable $CD4^+$ T cell counts, and no evidence of clinical diseases or mortality by day 420 after challenge. This finding is the second demonstration, following the protective result of live attenuated SIV vaccine in SIVmac-rhesus monkey model, which was known to have safety problem. So, our DNA vaccines could give a significant impact on HIV-1 epidemic by slowing or stopping the spread of HIV-1, leading to eventual eradication of HIV-1 and AIDS in the population.

Effects of Addition of Sugars on the Stability of Hepatitis B Virus Vaccine (당첨가가 B형 간염 바이러스 백신의 안정성에 미치는 영향)

  • Seong, In-Wha
    • The Journal of Korean Society of Virology
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    • v.27 no.2
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    • pp.143-149
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    • 1997
  • Most of the current licenced hepatitis B vaccines are being produced by recombinant DNA technology in large fermentation cultures of Saccharomyces cerevisiae of yeast cells which carry the gene coded for hepatitis B virus surface antigen. These vaccines are proved very effective clinically and the immunogenicity of vaccines could be maintained for a long time under refrigeration. To develope the stabilizer that could increase the stability of hepatitis B virus vaccine which could be stored for a long period at room temperature or higher conditions, glucose, lactose and sucrose solutions in phosphate buffered saline were added into hepatitis B vaccine respectively to make 2.5%, 5%, 7.5% and 10% final concentration in vaccines. These sugar-vaccine mixtures were stored at room temperature for one month, two months and three months respectively and then inoculated into ICR mice intramuscularly. On the fourteenth day after inoculation, mice were bled and sera were tested for the evaluation of efficacies of vaccines. The results showed that 5% glucose, 7.5% lactose and sucrose increased the stability of vaccines in some degree and this method could be applied for the production of other viral vaccines and bacterial vaccines.

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New trends of vaccine development: Recombinant vaccinia viruses (expression vectors) as vaccines (Vaccine개발(開發)의 새로운 동향(動向) : Vaccinia virus를 발견(發見) vector로 이용하는 재조합(再組合) 생(生)vaccine의 작성(作成))

  • Kim, Uh-ho
    • Korean Journal of Veterinary Research
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    • v.29 no.3
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    • pp.407-416
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    • 1989
  • The prospect of live vaccines consisting of genetically modified vaccinia virus expressing foreign genes is exciting, but important issues concerning safety and efficacy need to resolved. Vaccinia virus (VV) is an efficient expression vector with broad host range infectivity and large DNA capacity. This vector has been particularly useful for identifying target antigens for humoral and cell-mediated immunity. The WHO smallpox eradication program, involving the extensive use of VV vaccines, resulted in the late 1970s in the elimination of one of the world's most feared diseases. This achievement is a triumph for preventive medicine and for international collaboration in public health. In 1980, WHO recommended that the routine use of smallpox vaccine should be stopped. Against this background, the prospect of li ve vaccines consisting of genetically modified VV expressing foreign antigens arising from the work of Moss, and Paoletti and their colleagues in 1982 has been greeted with enthusiasm. These investigators have shown that genes coding for immunogenic proteins can be inserted into VV DNA without impairing the ability of the virus to grow in cell culture. Moreover experimental animals infected with VV recombinants containing genes coding for a variety of immunizing proteins have been shown to be protected against challenge infection with the corresponding infectious agent. In this communication, I describe current progress in the construction of a novel plasmid vector that facilitate the insertion and expression of foreign genes in VV as well as the selection of recombinants.

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The Reverse Proteomics for Identification of Tumor Antigens

  • Lee, Sang-Yull;Jeoung, Doo-Il
    • Journal of Microbiology and Biotechnology
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    • v.17 no.6
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    • pp.879-890
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    • 2007
  • The identification of tumor antigens is essential for the development of anticancer therapeutic vaccines and clinical diagnosis of cancer. SEREX (serological analysis of recombinant cDNA expression libraries) has been used to identify such tumor antigens by screening sera of patients with cDNA expression libraries. SEREX-defined antigens provide markers for the diagnosis of cancers. Potential diagnostic values of these SEREX-defined antigens have been evaluated. SEREX is also a powerful method for the development of anticancer therapeutics. The development of anticancer vaccines requires that tumor antigens can elicit antigen-specific antibodies or T lymphocytes. More than 2,000 antigens have been discovered by SEFEX. Peptides derived from some of these antigens have been evaluated in clinical trials. This review provides information on the application of SEREX for identification of tumor-associated antigens (TAA) for the development of cancer diagnostics and anticancer therapeutics.

Distinct Humoral and Cellular Immunity Induced by Alternating Prime-boost Vaccination Using Plasmid DNA and Live Viral Vector Vaccines Expressing the E Protein of Dengue Virus Type 2

  • George, Junu A.;Eo, Seong-Kug
    • IMMUNE NETWORK
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    • v.11 no.5
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    • pp.268-280
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    • 2011
  • Background: Dengue virus, which belongs to the Flavivirus genus of the Flaviviridae family, causes fatal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with infection risk of 2.5 billion people worldwide. However, approved vaccines are still not available. Here, we explored the immune responses induced by alternating prime-boost vaccination using DNA vaccine, adenovirus, and vaccinia virus expressing E protein of dengue virus type 2 (DenV2). Methods: Following immunization with DNA vaccine (pDE), adenovirus (rAd-E), and/or vaccinia virus (VV-E) expressing E protein, E protein-specific IgG and its isotypes were determined by conventional ELISA. Intracellular CD154 and cytokine staining was used for enumerating CD4+ T cells specific for E protein. E protein-specific CD8+ T cell responses were evaluated by in vivo CTL killing activity and intracellular IFN-${\gamma}$ staining. Results: Among three constructs, VV-E induced the most potent IgG responses, Th1-type cytokine production by stimulated CD4+ T cells, and the CD8+ T cell response. Furthermore, when the three constructs were used for alternating prime-boost vaccination, the results revealed a different pattern of CD4+ and CD8+ T cell responses. i) Priming with VV-E induced higher E-specific IgG level but it was decreased rapidly. ii) Strong CD8+ T cell responses specific for E protein were induced when VV-E was used for the priming step, and such CD8+ T cell responses were significantly boosted with pDE. iii) Priming with rAd-E induced stronger CD4+ T cell responses which subsequently boosted with pDE to a greater extent than VV-E and rAd-E. Conclusion: These results indicate that priming with live viral vector vaccines could induce different patterns of E protein-specific CD4+ and CD8+ T cell responses which were significantly enhanced by booster vaccination with the DNA vaccine. Therefore, our observation will provide valuable information for the establishment of optimal prime-boost vaccination against DenV.