Relevant bibliographies by topics / DNA vaccines

Academic literature on the topic 'DNA vaccines'

Author: Grafiati
Published: 4 June 2021
Last updated: 25 May 2024

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Journal articles on the topic "DNA vaccines"

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Omaji, G. O., T. M. Anakaa, and L. E. Ilouno. "DNA VACCINES: CHALLENGES AND APPROACHES." FUDMA JOURNAL OF SCIENCES 5, no. 4 (January 28, 2022): 216–21. http://dx.doi.org/10.33003/fjs-2021-0504-808.

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Since the discovery of the first vaccine about 200 years ago, improvement in vaccine development approaches has occurred over the years. Most notably, the emergence of DNA vaccines. DNA vaccines can evoke both humoral and cell mediated immunity, they are safe and have several advantages over other vaccines types. Despite this, poor immunogenicity produced by DNA vaccines in humans has called for novel strategies. This review highlight ways to improve the efficacy of DNA vaccines through plasmid modification, delivery systems, prime boost and addition of adjuvants. The review also discusses the potential of DNA vaccine in pandemic settings such as that of corona virus disease 2019 (COVID-19)
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Tuchkov, I. V., and A. K. Nikiforov. "Antirabies DNA Immunization." Problems of Particularly Dangerous Infections, no. 2(104) (April 20, 2010): 74–77. http://dx.doi.org/10.21055/0370-1069-2010-2(104)-74-77.

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Cited are literary data related to the development of DNA vaccines against rabies virus. Research results regarding gene vaccination of different models of laboratory animals and different ways of vaccine introduction are presented. Possibility to potentiate immunogenicity of DNA vaccines using adjuvants and cytokines is considered. Ways of improving of polynucleotide vaccines are discussed.
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&NA;. "DNA Vaccines—“Designer Vaccines”?" Infectious Diseases in Clinical Practice 9, no. 2 (February 2000): 41–42. http://dx.doi.org/10.1097/00019048-200009020-00003.

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Pushko, Peter, Igor S. Lukashevich, Dylan M. Johnson, and Irina Tretyakova. "Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses." Viruses 16, no. 3 (March 10, 2024): 428. http://dx.doi.org/10.3390/v16030428.

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Single-dose, immunogenic DNA (iDNA) vaccines coding for whole live-attenuated viruses are reviewed. This platform, sometimes called immunization DNA, has been used for vaccine development for flavi- and alphaviruses. An iDNA vaccine uses plasmid DNA to launch live-attenuated virus vaccines in vitro or in vivo. When iDNA is injected into mammalian cells in vitro or in vivo, the RNA genome of an attenuated virus is transcribed, which starts replication of a defined, live-attenuated vaccine virus in cell culture or the cells of a vaccine recipient. In the latter case, an immune response to the live virus vaccine is elicited, which protects against the pathogenic virus. Unlike other nucleic acid vaccines, such as mRNA and standard DNA vaccines, iDNA vaccines elicit protection with a single dose, thus providing major improvement to epidemic preparedness. Still, iDNA vaccines retain the advantages of other nucleic acid vaccines. In summary, the iDNA platform combines the advantages of reverse genetics and DNA immunization with the high immunogenicity of live-attenuated vaccines, resulting in enhanced safety and immunogenicity. This vaccine platform has expanded the field of genetic DNA and RNA vaccines with a novel type of immunogenic DNA vaccines that encode entire live-attenuated viruses.
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Srivastava, Indresh K., and Manmohan Singh. "DNA Vaccines." International Journal of Pharmaceutical Medicine 19, no. 1 (2005): 15–28. http://dx.doi.org/10.2165/00124363-200519010-00004.

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Lai, Wayne C., and Michael Bennett. "DNA Vaccines." Critical Reviews™ in Immunology 18, no. 5 (1998): 449–84. http://dx.doi.org/10.1615/critrevimmunol.v18.i5.30.

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Sung, Seung Yong. "DNA Vaccines." Journal of the Korean Medical Association 40, no. 1 (1997): 132. http://dx.doi.org/10.5124/jkma.1997.40.1.132.

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Reyes-Sandoval, Arturo, and Hildegund Ertl. "DNA Vaccines." Current Molecular Medicine 1, no. 2 (May 1, 2001): 217–43. http://dx.doi.org/10.2174/1566524013363898.

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Subramaniam, Geetha. "DNA Vaccines." Journal of Health and Translational Medicine 3, no. 1 (December 28, 1998): 18–21. http://dx.doi.org/10.22452/jummec.vol3no1.4.

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Spiegelberg, H. L., and E. Raz. "DNA vaccines." Allergy 54, s56 (October 1999): 47–48. http://dx.doi.org/10.1111/j.1398-9995.1999.tb04443.x.

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Dissertations / Theses on the topic "DNA vaccines"

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Farfan, Arribas Diego Jose. "DNA Vaccines Against HIV-1: Augmenting Immunogenicity of gp120." Link to electronic thesis, 2002. http://www.wpi.edu/Pubs/ETD/Available/etd-0107102-160706/.

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Parker, Christopher S. "Effect of a codon optimized DNA prime on induction of anti-influenza protective antibodies." Worcester, Mass. : Worcester Polytechnic Institute, 2007. http://www.wpi.edu/Pubs/ETD/Available/etd-040907-100839/.

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Bandholtz, Lisa Charlotta. "DNA vaccines and bacterial DNA in immunity /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-340-6/.

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Grubb, Kimberley L. "A genomic approach to the identification of novel malaria vaccine antigens /." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98715.

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As the number of drug-resistant malaria parasites continues to grow, pressure is increasing to find an effective, cross-protective, multi-valent malaria vaccine (32). Expression library immunisation is an un-biased screening technique that leads to the identification of novel, protective antigens that can be administered as components of a multivalent DNA vaccine (9, 50, 75, 86, 92). Here, a P. c. adami DS expression library has been evaluated as a malaria vaccine in mice, and several subpools of cross-protective plasmids have been identified. Upon vaccination with these plasmid subpools, mice demonstrate significantly lower mean cumulative parasitemia values than control vaccinated mice, when challenged with avirulent heterologous P. c. adami DK parasites. These cross-protective responses correlate with the induction of opsonizing antibodies against infected red blood cells and the production of IFN-gamma by T-cells. The determination of P. c. adami antigens capable of inducing strain-transcending immunity implies the identification of orthologues in the P. falciparum genome that may be applied as components of a human malaria vaccine.
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Chen, Caleb Gonshen. "DNA-based vaccines against cancer." Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405968.

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Rainczuk, Adam 1976. "Evaluation of DNA vaccine targeting strategies and expression library immunisation against lethal erythrocytic stage Malaria." Monash University, Dept. of Biochemistry and Molecular Biology, 2003. http://arrow.monash.edu.au/hdl/1959.1/5685.

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Roos, Anna-Karin. "Delivery of DNA vaccines against cancer /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-895-9/.

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Triyatni, Miriam. "Studies on the protective and therapeutic efficacy of duck hepatitis B virus vaccines /." Title page, table of contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09pht842.pdf.

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Thesis (Ph. D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999.
Copies of author's previously published article inserted onto back cover. Includes bibliographical references (leaves 164-187).
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Busch, Marc Gregory. "Evaluation of different SIV plasmid DNA vaccines : a model for HIV vaccine development /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2004. http://uclibs.org/PID/11984.

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Hobson, Philip Stanley. "Optimising the efficacy of plasmid DNA vaccines." Thesis, King's College London (University of London), 2004. https://kclpure.kcl.ac.uk/portal/en/theses/optimising-the-efficacy-of-plasmid-dna-vaccines(fd48c033-ff46-4c9b-b3cb-dc63c02c7824).html.

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Books on the topic "DNA vaccines"

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Lowrie, Douglas B., and Robert Whalen. DNA Vaccines. New Jersey: Humana Press, 1999. http://dx.doi.org/10.1385/1592596886.

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Janet, Brandsma L., Shen L. Hong, and Saltzman W. Mark. DNA Vaccines. New Jersey: Humana Press, 2006. http://dx.doi.org/10.1385/1597451681.

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Ertl, Hildegund C. J. DNA Vaccines. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4615-0105-3.

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Rinaldi, Monica, Daniela Fioretti, and Sandra Iurescia, eds. DNA Vaccines. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0410-5.

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Sousa, Ângela, ed. DNA Vaccines. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-0872-2.

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J, Ertl Hildegund C., ed. DNA vaccines. Georgetown, Tex: Landes bioscience/Eurekah.com, 2003.

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Gene vaccines. Wien: Springer, 2012.

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Donnelly, Erin C., and Arthur M. Dixon. DNA vaccines: Types, advantages, and limitations. New York: Nova Biomedical Books, 2011.

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P, Talwar G., Rao K. V. S, and Chauhan V. S, eds. Recombinant and synthetic vaccines. New Delhi: Narosa Pub. House, 1994.

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Mark, Saltzman W., Shen Hong 1972-, and Brandsma Janet L, eds. DNA vaccines: Methods and protocols. 2nd ed. Totowa, N.J: Humana Press, 2006.

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Book chapters on the topic "DNA vaccines"

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Liu, M. A., T. M. Fu, J. J. Donnelly, M. J. Caulfield, and J. B. Ulmer. "DNA Vaccines." In Advances in Experimental Medicine and Biology, 187–91. Boston, MA: Springer US, 1998. http://dx.doi.org/10.1007/978-1-4615-5355-7_21.

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Donnelly, John J. "DNA Vaccines." In New Bacterial Vaccines, 30–44. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4615-0053-7_3.

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Bradley, Eric S., and Douglas G. McNeel. "DNA Vaccines." In Cancer Therapeutic Targets, 183–98. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4419-0717-2_130.

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Biering, Eirik, and Kira Salonius. "DNA Vaccines." In Fish Vaccination, 47–55. Chichester, UK: John Wiley & Sons, Ltd, 2014. http://dx.doi.org/10.1002/9781118806913.ch5.

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Bereta, Michael, and Howard L. Kaufman. "DNA Vaccines." In Handbook of Cancer Vaccines, 225–48. Totowa, NJ: Humana Press, 2004. http://dx.doi.org/10.1007/978-1-59259-680-5_16.

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Novicki, Deborah L. "DNA Vaccines." In Encyclopedia of Immunotoxicology, 279–82. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-54596-2_396.

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Bradley, Eric S., and Douglas G. McNeel. "DNA Vaccines." In Cancer Therapeutic Targets, 1–16. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4614-6613-0_130-1.

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Mayrhofer, Peter, and Michaela Iro. "Minicircle-DNA." In Gene Vaccines, 297–310. Vienna: Springer Vienna, 2011. http://dx.doi.org/10.1007/978-3-7091-0439-2_15.

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Hilleman, Maurice R. "Overview of Vaccinology in Historic and Future Perspective." In DNA Vaccines, 1–38. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4615-0105-3_1.

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Chambers, M. A., H. M. Vordermeier, R. G. Hewinson, and D. B. Lowrie. "DNA Vaccines Against Bacterial Pathogens." In DNA Vaccines, 161–94. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4615-0105-3_10.

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Conference papers on the topic "DNA vaccines"

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Domach, M. M., S. A. Khan, and A. A. Ataai. "Unleashed DNA production for transfection, vaccines, or labeling." In 2015 41st Annual Northeast Biomedical Engineering Conference (NEBEC). IEEE, 2015. http://dx.doi.org/10.1109/nebec.2015.7117038.

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Kisakov, D. N., L. A. Kisakova, M. B. Borgoyakova, E. V. Starostina, A. M. Zadorozhny, E. V. Tigeeva, V. A. Yakovlev, A. P. Rudometov, L. I. Karpenko, and A. A. Ilyichev. "PHYSICAL METHODS FOR THE DELIVERY OF EXPERIMENTAL DNA- AND MRNA-VACCINES." In X Международная конференция молодых ученых: биоинформатиков, биотехнологов, биофизиков, вирусологов и молекулярных биологов — 2023. Novosibirsk State University, 2023. http://dx.doi.org/10.25205/978-5-4437-1526-1-181.

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The immunogenic and protective properties of DNA and mRNA vaccines were studied in BALB/c mice immunized by physical methods of administration (electroporation and jet injection) in this study. It has been shown that the delivery methods used induce the formation of a high level of humoral and T-cell immune response, providing protective immunity against the SARS-CoV-2.
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Greenland, John, Thomas Rodgers, and Norman Letvin. "Lung-targeted Plasmid DNA Vaccines Induce Potent Cellular Immune Responses." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a3782.

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Bordoloi, Devivasha, Peng Xiao, Hyeree Choi, Michelle Ho, Alfredo Perales-Puchalt, Makan Khoshnejad, J. Joseph Kim, et al. "Abstract 1915: Novel synthetic DNA vaccines in prostate cancer immunotherapy." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1915.

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Figueiredo, Lara, Cecilia C. R. Calado, Antonio J. Almeida, and Lidia M. D. Goncalves. "Protein and DNA nanoparticulate multiantigenic vaccines against H. pylori: In vivo evaluation." In 2012 IEEE 2nd Portuguese Meeting in Bioengineering (ENBENG). IEEE, 2012. http://dx.doi.org/10.1109/enbeng.2012.6331366.

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Lan, Keng-Hsueh, Ming-Feng Wei, Keng-Li Lan, Ann-Lii Cheng, and Sung-Hsin Kuo. "Abstract C102: Combination of immune checkpoints DNA vaccines and radiation enhances melanoma control." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; November 5-9, 2015; Boston, MA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1535-7163.targ-15-c102.

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Sérgio, Sarah, Gabriela Caldas, Natália Souza, Renata Fernandes, Ana Fernandes, Santuza Teixeira, Ricardo Gazzinelli, Flávio Fonseca, and Diego Ferreira. "Development and comparison of potential DNA and mRNA vaccines for Dengue serotype 2." In International Symposium on Immunobiologicals. Instituto de Tecnologia em Imunobiológicos, 2023. http://dx.doi.org/10.35259/isi.2023_57965.

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Rekoske, Brian T., Viswa T. Colluru, and Douglas G. McNeel. "Abstract CN04-03: DNA vaccines as treatment for prostate cancer - understanding mechanisms of resistance." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; November 5-9, 2015; Boston, MA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1535-7163.targ-15-cn04-03.

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Lan, Keng-Hsueh, Raghava Sriramaneni, Justin C. Jagodinsky, Claire Baniel, Amy Erbe-Gurel, Jacquelyn A. Hank, Sung-Hsin Kuo, Keng-Li Lan, and Zachary S. Morris. "Abstract 4055: Immune checkpoint DNA vaccines enhance anti-tumor immunity in murine melanoma model." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-4055.

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Facciabene, Andrea, John Facciponte, and George Coukos. "Abstract LB-197: Tumor vasculature associated marker as a target for recombinant DNA based vaccines." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-lb-197.

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Reports on the topic "DNA vaccines"

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Kwak, Larry W. Second-Generation Therapeutic DNA Lymphoma Vaccines. Fort Belvoir, VA: Defense Technical Information Center, May 2008. http://dx.doi.org/10.21236/ada485134.

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Kwak, Larry W. Second Generation Therapeutic DNA Lymphoma Vaccines. Fort Belvoir, VA: Defense Technical Information Center, May 2010. http://dx.doi.org/10.21236/ada540718.

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Kwak, Larry W. Second-Generation Therapeutic DNA Lymphoma Vaccines. Fort Belvoir, VA: Defense Technical Information Center, May 2009. http://dx.doi.org/10.21236/ada504992.

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Research, Gratis. Vaccines Through History: Smallpox to COVID-19. Gratis Research, March 2021. http://dx.doi.org/10.47496/gr.blog.011.

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More recently, as genomes turned out to be promptly decodable, scientists have developed proficient knowledge at developing vaccines that depend on extraction of RNA or DNA from microbes and injecting these into the body.
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Palmer, Guy, Varda Shkap, Wendy Brown, and Thea Molad. Control of bovine anaplasmosis: cytokine enhancement of vaccine efficacy. United States Department of Agriculture, March 2007. http://dx.doi.org/10.32747/2007.7695879.bard.

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Anaplasmosis an arthropod-born disease of cattle caused by the rickettsia Anaplasma marginale and is an impediment to efficient production of healthy livestock in both Israel and the United States. Currently the only effective vaccines are derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Consequently development of a safe, effective vaccine is a high priority. In this collaborative project we focused on two approaches to vaccine development. The first focused o n improving antigen delivery to livestock and specifically examined how DNA vaccines could be improved to enhance priming and expansion of the immune response. This research resulted in development and testing of two novel vaccine delivery systems--one that targeted antigen spread among dendritic cells (the key cell in priming immune responses and a follow-on construct that also specifically targeted antigen to the endosomal-lysosomal compartment the processing organelle within the dendritic cell that directs vaccine antigen to the MHC class ll-CD4* T cell priming pathway). The optimized construct targeting vaccine antigen to the dendritic cell MHC class II pathway was tested for ability to prime A. marginale specific immune responses in outbred cattle. The results demonstrated both statistically significant effects of priming with a single immunization, continued expansion of the primary immune response including development of high affinity lgG antibodies and rapid recall of the memory response following antigen challenge. This portion of the study represented a significant advance in vaccine delivery for livestock. Importantly the impact of these studies is not limited to A. marginale a s the targeting motifs are optimized for cattle and can be adapted to other cattle vaccinations by inserting a relevant pathogen-specific antigen. The second approach (which represented an addition to the project for which approval was requested as part of the first annual report) was a comparative approach between A . marginale and the Israel A . centrale vaccines train. This addition was requested as studies on Major Surface Protein( MSP)- 2 have shown that this antigen is highly antigenically variable and presented solely as a "static vaccine" antigen does not give cross-strain immunity. In contrast A. . centrale is an effective vaccine which Kimron Veterinary institute has used in the field in Israel for over 50 years. Taking advantage of this expertise, a broad comparison of wild type A. marginale and vaccine strain was initiated. These studies revealed three primary findings: i) use of the vaccine is associated with superinfection, but absence of clinical disease upon superinfection with A. marginale; ii) the A. centrale vaccine strain is not only less virulent but transmission in competent in Dermacentor spp. ticks; and iii) some but not all MSPs are conserved in basic orthologous structure but there are significant polymorphisms among the strains. These studies clearly indicated that there are statistically significant differences in biology (virulence and transmission) and provide a clear path for mapping of biology with the genomes. Based on these findings, we initiated complete genome sequencing of the Israel vaccine strain (although not currently funded by BARD) and plant to proceed with a comparative genomics approach using already sequenced wild-type A. marginale. These findings and ongoing collaborative research tie together filed vaccine experience with new genomic data, providing a new approach to vaccine development against a complex pathogen.
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Grubman, Marvin J., Yehuda Stram, Peter W. Mason, and Hagai Yadin. Development of an Empty Viral Capsid Vaccine against Foot and Mouth Disease. United States Department of Agriculture, August 1995. http://dx.doi.org/10.32747/1995.7570568.bard.

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Foot-and-mouth disease (FMD), a highly infectious viral disease of cloven-hoofed animals, is economically the most important disease of domestic animals. Although inactivated FMD vaccines have been succesfully used as part of comprehensive eradication programs in Western Europe, there are a number of concerns about their safety. In this proposal, we have attempted to develop a new generation of FMD vaccines that addresses these concerns. Specifically we have cloned the region of the viral genome coding for the structural proteins and the proteinase responsible for processing of the structural protein precursor into both a DNA vector and a replication-deficient human adenovirus. We have demonstrated the induction of an FMDV-specific immune response and a neutralizing antibody response with the DNA vectors in mice, but preliminary potency and efficacy studies in swine are variable. However, the adenovirus vector induces a significant and long-lived neutralizing antibody response in mice and most importantly a neutralizing and protective response in swine. These results suggest that the empty capsid approach is a potential alternative to the current vaccination strategy.
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Hui, Sek-Wen. Delivering DNA Vaccine by Transdermal Electroporation. Fort Belvoir, VA: Defense Technical Information Center, August 2002. http://dx.doi.org/10.21236/ada409785.

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Hui, Sek-Wen. Delivering DNA Vaccine by Transdermal Electroporation. Fort Belvoir, VA: Defense Technical Information Center, August 2003. http://dx.doi.org/10.21236/ada419796.

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Eldar, Avigdor, and Donald L. Evans. Streptococcus iniae Infections in Trout and Tilapia: Host-Pathogen Interactions, the Immune Response Toward the Pathogen and Vaccine Formulation. United States Department of Agriculture, December 2000. http://dx.doi.org/10.32747/2000.7575286.bard.

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In Israel and in the U.S., Streptococcus iniae is responsible for considerable losses in various fish species. Poor understanding of its virulence factors and limited know-how-to of vaccine formulation and administration are the main reasons for the limited efficacy of vaccines. Our strategy was that in order to Improve control measures, both aspects should be equally addressed. Our proposal included the following objectives: (i) construction of host-pathogen interaction models; (ii) characterization of virulence factors and immunodominant antigens, with assessment of their relative importance in terms of protection and (iii) genetic identification of virulence factors and genes, with evaluation of the protective effect of recombinant proteins. We have shown that two different serotypes are involved. Their capsular polysaccharides (CPS) were characterized, and proved to play an important role in immune evasion and in other consequences of the infection. This is an innovative finding in fish bacteriology and resembles what, in other fields, has become apparent in the recent years: S. iniae alters surface antigens. By so doing, the pathogen escapes immune destruction. Immunological assays (agar-gel immunodiffusion and antibody titers) confirmed that only limited cross recognition between the two types occurs and that capsular polysaccharides are immunodominant. Vaccination with purified CPS (as an acellular vaccine) results in protection. In vitro and ex-vivo models have allowed us to unravel additional insights of the host-pathogen interactions. S. iniae 173 (type II) produced DNA fragmentation of TMB-8 cells characteristic of cellular necrosis; the same isolate also prevented the development of apoptosis in NCC. This was determined by finding reduced expression of phosphotidylserine (PS) on the outer membrane leaflet of NCC. NCC treated with this isolate had very high levels of cellular necrosis compared to all other isolates. This cellular pathology was confirmed by observing reduced DNA laddering in these same treated cells. Transmission EM also showed characteristic necrotic cellular changes in treated cells. To determine if the (in vitro) PCD/apoptosis protective effects of #173 correlated with any in vivo activity, tilapia were injected IV with #173 and #164 (an Israeli type I strain). Following injection, purified NCC were tested (in vitro) for cytotoxicity against HL-60 target cells. Four significant observations were made : (i) fish injected with #173 had 100-400% increased cytotoxicity compared to #164 (ii) in vivo activation occurred within 5 minutes of injection; (iii) activation occurred only within the peripheral blood compartment; and (iv) the isolate that protected NCC from apoptosis in vitro caused in vivo activation of cytotoxicity. The levels of in vivo cytotoxicity responses are associated with certain pathogens (pathogen associated molecular patterns/PAMP) and with the tissue of origin of NCC. NCC from different tissue (i.e. PBL, anterior kidney, spleen) exist in different states of differentiation. Random amplified polymorphic DNA (RAPD) analysis revealed the "adaptation" of the bacterium to the vaccinated environment, suggesting a "Darwinian-like" evolution of any bacterium. Due to the selective pressure which has occurred in the vaccinated environment, type II strains, able to evade the protective response elicited by the vaccine, have evolved from type I strains. The increased virulence through the appropriation of a novel antigenic composition conforms with pathogenic mechanisms described for other streptococci. Vaccine efficacy was improved: water-in-oil formulations were found effective in inducing protection that lasted for a period of (at least) 6 months. Protection was evaluated by functional tests - the protective effect, and immunological parameters - elicitation of T- and B-cells proliferation. Vaccinated fish were found to be resistant to the disease for (at least) six months; protection was accompanied by activation of the cellular and the humoral branches.
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10

Bercovier, Herve, Raul Barletta, and Shlomo Sela. Characterization and Immunogenicity of Mycobacterium paratuberculosis Secreted and Cellular Proteins. United States Department of Agriculture, January 1996. http://dx.doi.org/10.32747/1996.7573078.bard.

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Our long-term goal is to develop an efficient acellular vaccine against paratuberculosis based on protein antigen(s). A prerequisite to achieve this goal is to analyze and characterize Mycobacterium paratuberculosis (Mpt) secreted and cellular proteins eliciting a protective immune response. In the context of this general objective, we proposed to identify, clone, produce, and characterize: the Mpt 85B antigen and other Mpt immunoreactive secreted proteins, the Mpt L7/L12 ribosomal protein and other immunoreactive cellular proteins, Mpt protein determinants involved in invasion of epithelial cells, and Mpt protein antigens specifically expressed in macrophages. Paratuberculosis is still a very serious problem in Israel and in the USA. In the USA, a recent survey evaluated that 21.6% of the dairy herd were infected with Mpt resulting in 200-250 million dollars in annual losses. Very little is known on the virulence factors and on protective antigens of Mpt. At present, the only means of controlling this disease are culling or vaccination. The current vaccines do not allow a clear differentiation between infected and vaccinated animals. Our long-term goal is to develop an efficient acellular paratuberculosis vaccine based on Mpt protein antigen(s) compatible with diagnostic tests. To achieve this goal it is necessary to analyze and characterize secreted and cellular proteins candidate for such a vaccine. Representative Mpt libraries (shuttle plasmid and phage) were constructed and used to study Mpt genes and gene products described below and will be made available to other research groups. In addition, two approaches were performed which did not yield the expected results. Mav or Mpt DNA genes that confer upon Msg or E. coli the ability to invade and/or survive within HEp-2 cells were not identified. Likewise, we were unable to characterize the 34-39 kDa induced secreted proteins induced by stress factors due to technical difficulties inherent to the complexity of the media needed to support substantial M. pt growth. We identified, isolated, sequenced five Mpt proteins and expressed four of them as recombinant proteins that allowed the study of their immunological properties in sensitized mice. The AphC protein, found to be up regulated by low iron environment, and the SOD protein are both involved in protecting mycobacteria against damage and killing by reactive oxygen (Sod) and nitrogen (AhpC) intermediates, the main bactericidal mechanisms of phagocytic cells. SOD and L7/L12 ribosomal proteins are structural proteins constitutively expressed. 85B and CFP20 are both secreted proteins. SOD, L7/L12, 85B and CFP20 were shown to induce a Th1 response in immunized mice whereas AphC was shown by others to have a similar activity. These proteins did not interfere with the DTH reaction of naturally infected cows. Cellular immunity provides protection in mycobacterial infections, therefore molecules inducing cellular immunity and preferentially a Th1 pathway will be the best candidate for the development of an acellular vaccine. The proteins characterized in this grant that induce a cell-mediated immunity and seem compatible with diagnostic tests, are good candidates for the construction of a future acellular vaccine.
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