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===Generations of vaccines=== [[File:Smallpox and anthrax vaccines of 447th Expeditionary Medical Squadron.jpg|thumb|Vials of smallpox and anthrax serum]] First generation vaccines are whole-organism vaccines{{snd}}either live and [[Attenuated virus|weakened]], or killed forms.<ref name="Alarcon1999">{{cite book|title=Advances in Parasitology Volume 42|vauthors=Alarcon JB, Waine GW, McManus DP|year=1999|isbn=978-0-12-031742-4|volume=42|pages=343–410|chapter=DNA Vaccines: Technology and Application as Anti-parasite and Anti-microbial Agents|doi=10.1016/S0065-308X(08)60152-9|pmid=10050276}}</ref> Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce [[Cytotoxic T cell|killer T-cell]] (T<sub>C</sub> or CTL) responses, [[Helper T cell|helper T-cell]] (T<sub>H</sub>) responses and antibody [[Immune system|immunity]]. However, attenuated forms of a [[pathogen]] can convert to a dangerous form and may cause disease in [[immunocompromised]] vaccine recipients (such as those with [[AIDS]]). While killed vaccines do not have this risk, they cannot generate specific killer T-cell responses and may not work at all for some diseases.<ref name="Alarcon1999" /> Second generation vaccines were developed to reduce the risks from live vaccines. These are subunit vaccines, consisting of specific [[protein]] antigens (such as [[tetanus]] or [[diphtheria]] [[toxoid]]) or [[Recombinant DNA|recombinant]] protein components (such as the hepatitis B surface [[antigen]]). They can generate T<sub>H</sub> and [[antibody]] responses, but not killer T cell responses.{{citation needed|date=January 2021}} [[RNA vaccine]]s and [[DNA vaccine]]s are examples of third generation vaccines.<ref name="Alarcon1999" /><ref name="Robinson2000">{{cite book|title=DNA vaccines for viral infections: basic studies and applications|vauthors=Robinson HL, Pertmer TM|year=2000|isbn=978-0-12-039855-3|series=Advances in Virus Research|volume=55|pages=1–74|doi=10.1016/S0065-3527(00)55001-5|pmid=11050940}}</ref><ref>{{cite web |last1=Naftalis |first1=Kramer Levin |last2=Royzman |first2=Frankel LLP-Irena |last3=Pineda |first3=ré |title=Third-Generation Vaccines Take Center Stage in Battle Against COVID-19 {{!}} Lexology |url=https://www.lexology.com/library/detail.aspx?g=04bdfa93-c8ea-4654-a5f1-c659fc4769c8 |website=www.lexology.com |date=30 November 2020 |access-date=24 January 2021 |archive-date=30 January 2021 |archive-url=https://web.archive.org/web/20210130052624/https://www.lexology.com/library/detail.aspx?g=04bdfa93-c8ea-4654-a5f1-c659fc4769c8 |url-status=live }}</ref> In 2016 a DNA vaccine for the [[Zika virus]] began testing at the [[National Institutes of Health]]. Separately, Inovio Pharmaceuticals and GeneOne Life Science began tests of a different DNA vaccine against Zika in Miami. Manufacturing the vaccines in volume was unsolved as of 2016.<ref>{{cite web|last=Regalado|first=Antonio|title=The U.S. government has begun testing its first Zika vaccine in humans|url=https://www.technologyreview.com/s/602073/us-government-starts-test-of-zika-vaccine-in-humans/?set=602081|access-date=6 August 2016|archive-date=21 August 2016|archive-url=https://web.archive.org/web/20160821082930/https://www.technologyreview.com/s/602073/us-government-starts-test-of-zika-vaccine-in-humans/?set=602081|url-status=live}}</ref> Clinical trials for DNA vaccines to prevent HIV are underway.<ref>{{cite journal|vauthors=Chen Y, Wang S, Lu S|date=February 2014|title=DNA Immunization for HIV Vaccine Development|journal=Vaccines|volume=2|issue=1|pages=138–159|doi=10.3390/vaccines2010138|pmc=4494200|pmid=26344472|doi-access=free}}</ref> [[mRNA vaccines]] such as [[BNT162b2]] were developed in the year 2020 with the help of [[Operation Warp Speed]] and massively deployed to combat the [[COVID-19 pandemic]]. In 2021, [[Katalin Karikó]] and [[Drew Weissman]] received Columbia University's Horwitz Prize for their pioneering research in mRNA vaccine technology.<ref>{{cite web|date=12 August 2021|title=Katalin Karikó and Drew Weissman Awarded Horwitz Prize for Pioneering Research on COVID-19 Vaccines|url=https://www.cuimc.columbia.edu/news/horwitz-prize-2021|access-date=7 September 2021|website=Columbia University Irving Medical Center|archive-date=16 August 2021|archive-url=https://web.archive.org/web/20210816131824/https://www.cuimc.columbia.edu/news/horwitz-prize-2021|url-status=live}}</ref>
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