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== History == {{See also|Vaccine#History}} Conventional vaccines contain either specific [[antigens]] from a pathogen, or attenuated viruses which stimulate an immune response in the vaccinated organism. DNA vaccines are members of the [[genetic vaccine]]s, because they contain a genetic information (DNA or RNA) that codes for the cellular production ([[protein biosynthesis]]) of an [[antigen]]. DNA vaccines contain DNA that codes for specific antigens from a pathogen. The DNA is injected into the body and taken up by cells, whose normal metabolic processes synthesize proteins based on the genetic code in the plasmid that they have taken up. Because these proteins contain regions of amino acid sequences that are characteristic of bacteria or viruses, they are recognized as foreign and when they are processed by the host cells and displayed on their surface, the immune system is alerted, which then triggers immune responses.<ref name="Alarcon1999">{{cite book | vauthors = Alarcon JB, Waine GW, McManus DP | volume = 42 | pages = 343β410 | year = 1999 | pmid = 10050276 | doi = 10.1016/S0065-308X(08)60152-9 | isbn = 9780120317424 | title = Advances in Parasitology Volume 42 | chapter = DNA Vaccines: Technology and Application as Anti-parasite and Anti-microbial Agents }}</ref><ref name="Robinson2000">{{cite book | vauthors = Robinson HL, Pertmer TM | title = DNA vaccines for viral infections: basic studies and applications | volume = 55 | pages = 1β74 | year = 2000 | pmid = 11050940 | doi = 10.1016/S0065-3527(00)55001-5 | isbn = 9780120398553 | series = Advances in Virus Research }}</ref> Alternatively, the DNA may be encapsulated in protein to facilitate cell entry. If this [[capsid]] protein is included in the DNA, the resulting vaccine can combine the potency of a live vaccine without reversion risks.{{Citation needed | date = October 2021 | reason = Besides needing to be verifiable, these last two sentences are also unclear. If the capsid protein is in the DNA, should the DNA itself still be encapsulated in the protein? Is the aforementioned capsid protein a virus protein or some other proteins?}} In 1983, [[Enzo Paoletti]] and Dennis Panicali at the [[New York Department of Health]] devised a strategy to produce [[recombinant DNA]] vaccines by using genetic engineering to transform ordinary [[smallpox vaccine]] into vaccines that may be able to prevent other diseases.<ref>{{cite journal | vauthors = White LO, Gibb E, Newham HC, Richardson MD, Warren RC | title = Comparison of the growth of virulent and attenuated strains of Candida albicans in the kidneys of normal and cortison-treated mice by chitin assay | journal = Mycopathologia | volume = 67 | issue = 3 | pages = 173β177 | date = July 1979 | pmid = 384256 | doi = 10.1007/bf00470753 | s2cid = 31914107 }}</ref> They altered the DNA of [[cowpox]] virus by inserting a gene from other viruses (namely [[Herpes simplex virus]], [[hepatitis B]] and [[influenza]]).<ref>{{cite journal | vauthors = Paoletti E, Lipinskas BR, Samsonoff C, Mercer S, Panicali D | title = Construction of live vaccines using genetically engineered poxviruses: biological activity of vaccinia virus recombinants expressing the hepatitis B virus surface antigen and the herpes simplex virus glycoprotein D | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 1 | pages = 193β197 | date = January 1984 | pmid = 6320164 | pmc = 344637 | doi = 10.1073/pnas.81.1.193 | doi-access = free | bibcode = 1984PNAS...81..193P }}</ref><ref>US Patent 4722848 - Method for immunizing animals with synthetically modified vaccinia virus</ref> In 1993, Jeffrey Ulmer and co-workers at [[Merck & Co.|Merck Research Laboratories]] demonstrated that direct injection of mice with plasmid DNA encoding a flu antigen protected the animals against subsequent experimental infection with influenza virus.<ref>{{cite journal | vauthors = Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A | display-authors = 6 | title = Heterologous protection against influenza by injection of DNA encoding a viral protein | journal = Science | volume = 259 | issue = 5102 | pages = 1745β1749 | date = March 1993 | pmid = 8456302 | doi = 10.1126/science.8456302 | bibcode = 1993Sci...259.1745U }}</ref> In 2016 a DNA vaccine for the [[Zika virus]] began testing in humans at the [[National Institutes of Health]]. The study was planned to involve up to 120 subjects aged between 18 and 35. Separately, [[Inovio Pharmaceuticals]] and [http://www.genels.com/en/ GeneOne Life Science] began tests of a different DNA vaccine against Zika in Miami. The NIH vaccine is injected into the upper arm under high pressure. Manufacturing the vaccines in volume remained unsolved as of August 2016.<ref name="mittr">{{Cite web|url=https://www.technologyreview.com/s/602073/us-government-starts-test-of-zika-vaccine-in-humans/?set=602081|title=The U.S. government has begun testing its first Zika vaccine in humans|last=Regalado|first=Antonio|access-date=2016-08-06|publisher=MIT Technology Review Magazine|date=2 August 2016}}</ref> Clinical trials for DNA vaccines to prevent HIV are underway.<ref>{{cite journal | vauthors = Chen Y, Wang S, Lu S | title = DNA Immunization for HIV Vaccine Development | journal = Vaccines | volume = 2 | issue = 1 | pages = 138β159 | date = February 2014 | pmid = 26344472 | pmc = 4494200 | doi = 10.3390/vaccines2010138 | doi-access = free }}</ref> In August 2021, Indian authorities gave emergency approval to ZyCoV-D. Developed by [[Cadila Healthcare]], it is the first DNA vaccine against [[COVID-19]].<ref name=":0">{{Cite web|date=2021-08-20|title=India gives emergency approval for world's first COVID-19 DNA vaccine|url=https://www.reuters.com/business/healthcare-pharmaceuticals/india-approves-zydus-cadilas-covid-19-vaccine-emergency-use-2021-08-20/|access-date=2021-08-22|website=Reuters|language=en}}</ref>
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