Editing Vaccine (section)

==Types==
[[File:WHO EN Vaccines Topics Race for a COVID-19 vaccine 01 12Jan2021.jpg|thumb|alt=Illustration with the text "There are three main approaches to making a vaccine: Using a whole virus or bacterium Parts that trigger the immune system Just the genetic material."|<!--[[wp:caption]] "Not every image ..."-->]]
Vaccines typically contain attenuated, inactivated or dead organisms or purified products derived from them. There are several types of vaccines in use.<ref>{{cite web|url = https://www.niaid.nih.gov/topics/vaccines/Pages/typesVaccines.aspx|title = Vaccine Types|publisher = [[NIAID|National Institute of Allergy and Infectious Diseases]]|date = 3 April 2012|access-date = 27 January 2015|url-status=live|archive-url = https://web.archive.org/web/20150905205720/http://www.niaid.nih.gov/topics/vaccines/Pages/typesVaccines.aspx|archive-date = 5 September 2015}}</ref> These represent different strategies used to try to reduce the risk of illness while retaining the ability to induce a beneficial immune response.

===Attenuated===
{{main|Attenuated vaccine}}

Some vaccines contain live, [[attenuated vaccine|attenuated]] microorganisms. Many of these are active [[viruses]] that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases [[yellow fever]], [[measles]], [[mumps]], and [[rubella]], and the bacterial disease [[typhoid]]. The live ''Mycobacterium [[tuberculosis]]'' vaccine developed by Calmette and Guérin is not made of a [[Infectious disease|contagious]] strain but contains a virulently modified strain called "[[Bacillus Calmette-Guérin|BCG]]" used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain ''[[Yersinia pestis]]'' EV is used for [[Plague (disease)|plague]] immunization. Attenuated vaccines have some advantages and disadvantages. Attenuated, or live, weakened, vaccines typically provoke more durable immunological responses. Attenuated vaccines also elicit a cellular and humoral response. However, they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease.<ref name="Bhattacharya">{{cite book | vauthors = Sinha JK, Bhattacharya S | title=A Text Book of Immunology | url=https://books.google.com/books?id=ytCNCbCWx8oC&pg=PA318 | format=Google Books Preview | publisher=Academic Publishers | isbn=978-81-89781-09-5 | page=318 | access-date=9 January 2014}}</ref>

===Inactivated===
{{main|Inactivated vaccine}}

Some vaccines contain microorganisms that have been killed or inactivated by physical or chemical means. Examples include IPV ([[polio vaccine]]), [[hepatitis&nbsp;A vaccine]], [[rabies vaccine]] and most [[influenza vaccines]].<ref>{{cite web|url=https://www.vaccines.gov/basics/types/index.html|title=Types of Vaccines |archive-url=https://web.archive.org/web/20170729161636/https://www.vaccines.gov/basics/types/index.html|archive-date=29 July 2017|url-status=live|access-date=19 October 2017}}</ref><ref name="historyofvaccines.org">{{cite web|url=https://www.historyofvaccines.org/content/articles/different-types-vaccines|title=Different Types of Vaccines |website=History of Vaccines |access-date=14 June 2019|archive-date=26 January 2019|archive-url=https://web.archive.org/web/20190126060918/https://www.historyofvaccines.org/content/articles/different-types-vaccines|url-status=live}}</ref>[[File:ReverseGeneticsFlu.svg|thumbnail|300px|[[Avian influenza|Avian flu]] vaccine development by [[reverse genetics]] techniques]]

===Toxoid===
{{main|Toxoid}}

[[Toxoid]] vaccines are made from inactivated toxic compounds that cause illness rather than the microorganism.<ref name="historyofvaccines.org"/> Examples of toxoid-based vaccines include [[tetanus]] and [[diphtheria]].<ref name="historyofvaccines.org" /> Not all toxoids are for microorganisms; for example, ''[[Crotalus atrox]]'' toxoid is used to vaccinate dogs against [[rattlesnake]] bites.<ref>{{cite web|url=http://coastalcarolinaresearch.com/types-of-vaccines/|title=Types of Vaccines|website=coastalcarolinaresearch.com|access-date=3 May 2019|archive-date=3 May 2019|archive-url=https://web.archive.org/web/20190503112746/http://coastalcarolinaresearch.com/types-of-vaccines/}}</ref>

===Subunit===
{{main|Subunit vaccine}}

Rather than introducing an inactivated or attenuated microorganism to an immune system (which would constitute a "whole-agent" vaccine), a [[Protein subunit|subunit]] vaccine uses a fragment of it to create an immune response. One example is the subunit vaccine against [[Hepatitis B#Virology|hepatitis{{spaces}}B]], which is composed of only the surface proteins of the virus (previously extracted from the [[blood serum]] of chronically infected patients but now produced by [[recombinant DNA|recombination]] of the viral genes into [[yeast]]).<ref>{{cite web|url=https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/vaccine-hepatitis-b-vaccine|title=A Look at Each Vaccine: Hepatitis B Vaccine|last=Philadelphia|first=The Children's Hospital of|date=18 August 2014|website=www.chop.edu|access-date=14 June 2019|archive-date=31 May 2019|archive-url=https://web.archive.org/web/20190531160201/https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/vaccine-hepatitis-b-vaccine|url-status=live}}</ref> Other examples include the [[Gardasil]] [[virus-like particle]] [[human papillomavirus]] (HPV) vaccine,<ref>{{cite web|url=https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html|title=HPV Vaccine {{!}} Human Papillomavirus {{!}} CDC|date=13 May 2019|website=www.cdc.gov|access-date=14 June 2019|archive-date=18 June 2019|archive-url=https://web.archive.org/web/20190618034022/https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html|url-status=live}}</ref> the [[hemagglutinin]] and [[neuraminidase]] subunits of the [[influenza]] virus,<ref name="historyofvaccines.org"/> and [[edible algae vaccine]]s. A subunit vaccine is being used for plague immunization.<ref>{{Cite journal|last1=Williamson|first1=E. D.|last2=Eley|first2=S. M.|last3=Griffin|first3=K. F.|last4=Green|first4=M.|last5=Russell|first5=P.|last6=Leary|first6=S. E.|last7=Oyston|first7=P. C.|last8=Easterbrook|first8=T.|last9=Reddin|first9=K. M.|date=December 1995|title=A new improved sub-unit vaccine for plague: the basis of protection|journal=FEMS Immunology and Medical Microbiology|volume=12|issue=3–4|pages=223–230|doi=10.1111/j.1574-695X.1995.tb00196.x|issn=0928-8244|pmid=8745007|doi-access=free}}</ref>

===Conjugate===
{{main|Conjugate vaccine}}

Certain bacteria have a polysaccharide [[Bacterial capsule|outer coat]] that is poorly [[immunogenic]]. By linking these outer coats to proteins (e.g., toxins), the [[immune system]] can be led to recognize the [[polysaccharide]] as if it were a protein antigen. This approach is used in the [[Hib vaccine|''Haemophilus influenzae'' type B vaccine]].<ref>{{cite web|url=http://www.globalhealthprimer.emory.edu/targets-technologies/polysaccharide-protein-conjugate-vaccines.html|title=Polysaccharide Protein Conjugate Vaccines|website=www.globalhealthprimer.emory.edu|access-date=14 June 2019|archive-date=23 June 2019|archive-url=https://web.archive.org/web/20190623043558/http://www.globalhealthprimer.emory.edu/targets-technologies/polysaccharide-protein-conjugate-vaccines.html|url-status=live}}</ref>

===Outer membrane vesicle===

[[Bacterial outer membrane vesicles|Outer membrane vesicles]] (OMVs) are naturally immunogenic and can be manipulated to produce potent vaccines. The best known OMV vaccines are those developed for [[Meningococcal vaccine#Serogroup B|serotype B meningococcal disease]].<ref name="vaccinology-guide">{{cite journal |vauthors=Pollard AJ, Bijker EM |title=A guide to vaccinology: from basic principles to new developments |journal=Nature Reviews Immunology |date=22 December 2020 |volume=21 |issue=2 |pages=83–100 |doi=10.1038/s41577-020-00479-7 |pmid=33353987 |pmc=7754704 |issn=1474-1741 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Pol L, Stork M, Ley P |date=11 November 2015 |title=Outer membrane vesicles as platform vaccine technology |journal=Biotechnology Journal |volume=10 |issue=11 |pages=1689–1706 |doi=10.1002/biot.201400395 |issn=1860-7314 |pmc=4768646 |pmid=26912077 }}</ref>

===Heterotypic===
{{main|Heterologous vaccine}}

[[Heterologous vaccine]]s also known as "Jennerian vaccines", are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of [[BCG vaccine]] made from ''[[Mycobacterium bovis]]'' to protect against [[tuberculosis]].<ref>{{cite journal|last=Scott|date=April 2004|title=Classifying Vaccines|url=http://www.bioprocessintl.com/multimedia/archive/00077/0204su03_77445a.pdf|url-status=live|journal=BioProcesses International|pages=14–23|archive-url=https://web.archive.org/web/20131212222400/http://www.bioprocessintl.com/multimedia/archive/00077/0204su03_77445a.pdf|archive-date=12 December 2013|access-date=9 January 2014}}</ref>

=== Genetic vaccine ===
{{main|Genetic vaccine}}

Genetic vaccines are based on the principle of uptake of a nucleic acid into cells, whereupon a protein is produced according to the nucleic acid template. This protein is usually the immunodominant antigen of the pathogen or a surface protein that enables the formation of neutralizing antibodies. The subgroup of genetic vaccines encompass viral vector vaccines, RNA vaccines and DNA vaccines.{{citation needed|date=January 2024}}

==== Viral vector ====
{{main|Viral vector vaccine}}

Viral vector vaccines use a safe [[virus]] to insert pathogen genes in the body to produce specific [[antigen]]s, such as surface [[protein]]s, to stimulate an [[immune response]].<ref>{{cite web |url=https://www.vaccines.gov/basics/types |title=Vaccine Types |website=Vaccines.org |publisher=Office of Infectious Disease of the [[United States Department of Health and Human Services]] |access-date=13 March 2021 |archive-date=23 May 2019 |archive-url=https://web.archive.org/web/20190523191043/https://www.vaccines.gov/basics/types |url-status=live }}</ref><ref>{{cite web |url=https://www.cdc.gov/vaccines/covid-19/hcp/viral-vector-vaccine-basics.html |title=Understanding and Explaining Viral Vector COVID-19 Vaccines |publisher=[[Centers for Disease Control and Prevention]] |access-date=13 March 2021 |archive-date=2 February 2021 |archive-url=https://web.archive.org/web/20210202160930/https://www.cdc.gov/vaccines/covid-19/hcp/viral-vector-vaccine-basics.html |url-status=live }}</ref> Viruses being researched for use as viral vectors include adenovirus, vaccinia virus, and [[Indiana vesiculovirus|VSV]].

====RNA====
{{main|RNA vaccine}}

An mRNA vaccine (or [[RNA vaccine]]) is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid [[nanoparticle]]s.<ref>{{cite web | last1=Garde | first1=Damian | last2=Feuerstein | first2=Adam | title=How nanotechnology helps mRNA Covid-19 vaccines work | website=STAT | date=1 November 2020 | url=https://www.statnews.com/2020/12/01/how-nanotechnology-helps-mrna-covid19-vaccines-work/ | access-date=21 December 2020 | archive-date=1 December 2020 | archive-url=https://web.archive.org/web/20201201210905/https://www.statnews.com/2020/12/01/how-nanotechnology-helps-mrna-covid19-vaccines-work/ | url-status=live }}</ref> Among the [[COVID-19 vaccine]]s are a number of RNA vaccines to combat the [[COVID-19 pandemic]] and some have been approved or have received [[emergency use authorization]] in some countries. For example, the [[Pfizer–BioNTech COVID-19 vaccine|Pfizer-BioNTech]] vaccine and [[Moderna COVID-19 vaccine|Moderna mRNA]] vaccine are approved for use in adults and children in the US.<ref>{{cite web | author=CDC | title=COVID-19 and Your Health | website=Centers for Disease Control and Prevention | date=11 February 2020 | url=https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html | access-date=21 December 2020 | archive-date=3 March 2021 | archive-url=https://web.archive.org/web/20210303003047/https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html | url-status=live }}</ref><ref>{{cite web | last=Banks | first=Marcus A. | title=What Are mRNA Vaccines, and Could They Work Against COVID-19? | website=Smithsonian Magazine | date=16 July 2020 | url=https://www.smithsonianmag.com/science-nature/mrna-vaccines-covid-19-180975330/ | access-date=21 December 2020 | archive-date=21 December 2020 | archive-url=https://web.archive.org/web/20201221010102/https://www.smithsonianmag.com/science-nature/mrna-vaccines-covid-19-180975330/ | url-status=live }}</ref><ref>{{cite web | last=Branswell | first=Helen | title=FDA grants authorization to Moderna's Covid-19 vaccine | website=STAT | date=19 December 2020 | url=https://www.statnews.com/2020/12/18/fda-eua-moderna-vaccine-covid19/ | access-date=21 December 2020 | archive-date=21 December 2020 | archive-url=https://web.archive.org/web/20201221163920/https://www.statnews.com/2020/12/18/fda-eua-moderna-vaccine-covid19/ | url-status=live }}</ref>

====DNA====
{{main|DNA vaccine}}

A DNA vaccine uses a [[DNA]] [[plasmid]] (pDNA)) that encodes for an antigenic protein originating from the pathogen upon which the vaccine will be targeted. pDNA is inexpensive, stable, and relatively safe, making it an excellent option for vaccine delivery.<ref>{{Cite web |last=Cuffari |first=Benedette |date=17 March 2021 |title=What is a DNA Vaccine? |url=https://www.news-medical.net/health/What-is-a-DNA-based-vaccine.aspx |access-date=14 January 2024 |website=News-Medical.net |archive-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114104703/https://www.news-medical.net/health/What-is-a-DNA-based-vaccine.aspx |url-status=live }}</ref>

This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture.<ref>{{Cite web |title=DNA Vaccines |url=https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/vaccines-quality/dna |access-date=14 January 2024 |website=[[World Health Organization]] (WHO) |archive-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114104704/https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/vaccines-quality/dna |url-status=live }}</ref>

===Experimental===
Many innovative vaccines are also in development and use.
* Dendritic cell vaccines combine [[dendritic cell]]s with antigens to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors<ref>{{cite journal | vauthors = Kim W, Liau LM | title = Dendritic cell vaccines for brain tumors | journal = Neurosurgery Clinics of North America | volume = 21 | issue = 1 | pages = 139–157 | date = January 2010 | pmid = 19944973 | pmc = 2810429 | doi = 10.1016/j.nec.2009.09.005 }}</ref> and are also tested in malignant melanoma.<ref name="pmid24872109">{{cite journal | vauthors = Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN | title = Clinical use of dendritic cells for cancer therapy | journal = The Lancet. Oncology | volume = 15 | issue = 7 | pages = e257–267 | date = June 2014 | pmid = 24872109 | doi = 10.1016/S1470-2045(13)70585-0 }}</ref>
* [[Recombinant DNA|Recombinant]] [[Viral vector vaccine|vector]]{{snd}}by combining the physiology of one microorganism and the [[DNA]] of another, immunity can be created against diseases that have complex infection processes. An example is the [[RVSV-ZEBOV vaccine]] licensed to Merck that is being used in 2018 to combat [[2017 Democratic Republic of the Congo Ebola virus outbreak|ebola in Congo]].<ref>{{cite news|last1=McKenzie|first1=David|title=Fear and failure: How Ebola sparked a global health revolution|url=https://edition.cnn.com/2018/05/26/health/ebola-outbreaks-west-africa-congo-revolution-mckenzie-intl/index.html|access-date=26 May 2018|publisher=CNN|date=26 May 2018|archive-date=26 August 2019|archive-url=https://web.archive.org/web/20190826101345/https://edition.cnn.com/2018/05/26/health/ebola-outbreaks-west-africa-congo-revolution-mckenzie-intl/index.html|url-status=live}}</ref>
* [[T-cell receptor]] peptide vaccines are under development for several diseases using models of [[Valley Fever]], [[stomatitis]], and [[atopic dermatitis]]. These peptides have been shown to modulate [[cytokine]] production and improve cell-mediated immunity.
* Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.<ref name="pmid19388175">{{cite journal | vauthors = Meri S, Jördens M, Jarva H | title = Microbial complement inhibitors as vaccines | journal = Vaccine | volume = 26 | pages = I113–117 | date = December 2008 | issue = Suppl 8 | pmid = 19388175 | doi = 10.1016/j.vaccine.2008.11.058 }}</ref>
* The use of [[plasmid]]s has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, in human studies, this approach has failed to provide clinically relevant benefit. The overall efficacy of plasmid DNA immunization depends on increasing the plasmid's [[immunogenicity]] while also correcting for factors involved in the specific activation of immune effector cells.<ref name="Lowe">{{cite book|author=Lowe|title=Plasmids: Current Research and Future Trends|publisher=Caister Academic Press|year=2008|isbn=978-1-904455-35-6|chapter=Plasmid DNA as Prophylactic and Therapeutic vaccines for Cancer and Infectious Diseases|chapter-url=http://www.horizonpress.com/pla|access-date=15 April 2008|archive-date=11 April 2008|archive-url=https://web.archive.org/web/20080411053922/http://www.horizonpress.com/pla|url-status=live}}</ref>
* [[Vector (epidemiology)|Bacterial vector]] – Similar in principle to [[viral vector vaccine]]s, but using bacteria instead.<ref name="vaccinology-guide"/>
* [[Antigen-presenting cell vaccine|Antigen-presenting cell]]<ref name="vaccinology-guide"/>
* Technologies which may allow rapid vaccine deployment in response to a [[Emerging infectious disease|novel pathogen]] include the use of [[virus-like particle]]s<ref>{{Cite web |last1=Chang |first1=Lee-Jah |last2=Blair |first2=Wade |date=11 December 2023 |title=Mimicking nature: Virus-like particles and the next generation of vaccines |url=https://www.astrazeneca.com/what-science-can-do/topics/technologies/virus-like-particles-next-generation-vaccines.html |website=AstraZeneca}}</ref> or protein nanoparticles.<ref>{{Cite web |last=Cambridge |first=University of |title='Quartet Nanocage' vaccine found effective against coronaviruses that haven't even emerged yet |url=https://phys.org/news/2024-05-quartet-nanocage-vaccine-effective-coronaviruses.html |access-date=6 May 2024 |website=phys.org }}</ref>
* [[Inverse vaccine]]s are vaccines that train the immune system to not respond to certain substances.

While most vaccines are created using inactivated or attenuated compounds from microorganisms, [[synthetic vaccine]]s are composed mainly or wholly of synthetic peptides, carbohydrates, or antigens.{{Citation needed|date=May 2024}}