Editing Vaccination (section)

== Safety ==
{{Further|Vaccine hesitancy|Vaccine adverse event}}
[[File:Global-smallpox-cases.png|thumb|Global [[smallpox]] cases from 1920 to 2010. Source: [[World Health Organization|WHO]]]]

=== Vaccine development and approval ===
Just like any medication or procedure, no vaccine can be 100% safe or effective for everyone because each person's body can react differently.<ref>{{Cite web|url=https://www.cdc.gov/vaccinesafety/ensuringsafety/history/index.html|title=History of Vaccine Safety History Ensuring Safety Vaccine Safety CDC|date=10 January 2019|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=12 March 2019|archive-date=28 March 2019|archive-url=https://web.archive.org/web/20190328070048/https://www.cdc.gov/vaccinesafety/ensuringsafety/history/index.html|url-status=live}}</ref><ref name="Chen-1998">{{cite journal | vauthors = Chen RT, Hibbs B | s2cid = 13364842 | title = Vaccine safety: current and future challenges | journal = Pediatric Annals | volume = 27 | issue = 7 | pages = 445–55 | date = July 1998 | pmid = 9677616 | doi = 10.3928/0090-4481-19980701-11 }}</ref> While minor [[side effect]]s, such as soreness or low grade fever, are relatively common, serious side effects are very rare and occur in about 1 out of every 100,000 vaccinations and typically involve [[Allergy|allergic reactions]] that can cause hives or difficulty breathing.<ref name="NIH-site-2019">{{Cite web|url=https://www.niaid.nih.gov/research/making-safe-vaccines|title=Making Safe Vaccines NIH: National Institute of Allergy and Infectious Diseases|website=www.niaid.nih.gov|access-date=12 March 2019|archive-date=28 March 2019|archive-url=https://web.archive.org/web/20190328065701/https://www.niaid.nih.gov/research/making-safe-vaccines|url-status=live}}</ref><ref name="USCDC-2018">{{Cite web|url=https://www.cdc.gov/vaccines/vac-gen/side-effects.htm|title=Vaccines: Vac-Gen/Side Effects|date=12 July 2018|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=12 March 2019|archive-date=17 March 2017|archive-url=https://web.archive.org/web/20170317050028/https://www.cdc.gov/vaccines/vac-gen/side-effects.htm|url-status=live}}</ref>

However, vaccines are the safest they ever have been in history and each vaccine undergoes rigorous clinical trials to ensure their safety and [[Vaccine efficacy|efficacy]] before approval by authorities such as the US [[Food and Drug Administration]] (FDA).<ref name="USCDC-2018b">{{Cite web|url=https://www.cdc.gov/vaccinesafety/ensuringsafety/index.html|title=Ensuring Vaccine Safety Ensuring Safety Vaccine Safety CDC|date=12 December 2018|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=12 March 2019|archive-date=12 March 2019|archive-url=https://web.archive.org/web/20190312165811/https://www.cdc.gov/vaccinesafety/ensuringsafety/index.html|url-status=live}}</ref>

Prior to human testing, vaccines are tested on [[cell culture]]s and the results modelled to assess how they will interact with the immune system.<ref name="NIH-site-2019" /><ref name="USCDC-2018b" /> During the next round of testing, researchers study vaccines in animals, including [[Mouse|mice]], [[rabbit]]s, [[guinea pig]]s, and [[monkey]]s.<ref name="NIH-site-2019" /> Vaccines that pass each of these stages of testing are then approved by the public health safety authority (FDA in the United States) to start a three-phase series of human testing, advancing to higher phases only if they are deemed safe and effective at the previous phase. The people in these trials participate voluntarily and are required to prove they understand the purpose of the study and the potential risks.<ref name="USCDC-2018b" />

During phase I trials, a vaccine is tested in a group of about 20 people with the primary goal of assessing the vaccine's safety.<ref name="NIH-site-2019" /> Phase II trials expand the testing to include 50 to several hundred people. During this stage, the vaccine's safety continues to be evaluated and researchers also gather data on the effectiveness and the ideal dose of the vaccine.<ref name="NIH-site-2019" /> Vaccines determined to be safe and efficacious then advance to phase III trials, which focuses on the efficacy of the vaccine in hundreds to thousands of volunteers. This phase can take several years to complete and researchers use this opportunity to compare the vaccinated volunteers to those who have not been vaccinated to highlight any true reactions to the vaccine that occur.<ref name="USCDC-2018b" />

If a vaccine passes all of the phases of testing, the manufacturer can then apply for license of the vaccine through the relevant regulatory authorities such as the FDA in US. Before regulatory authorities approve use in the general public, they extensively review the results of the clinical trials, safety tests, purity tests, and manufacturing methods and establish that the manufacturer itself is up to government standards in many other areas.<ref name="NIH-site-2019" /><ref name=":who_vac_dev">{{Cite press release |url=https://www.who.int/news-room/feature-stories/detail/how-are-vaccines-developed|title=How are vaccines developed? WHO|date=8 December 2020|website=[[World Health Organization]] (WHO)|access-date=26 October 2023|archive-date=26 October 2023|archive-url=https://web.archive.org/web/20231026062500/https://www.who.int/news-room/feature-stories/detail/how-are-vaccines-developed|url-status=live}}</ref>

After regulatory approval, the regulators continue to monitor the manufacturing protocols, batch purity, and the manufacturing facility itself. Additionally, vaccines also undergo phase IV trials, which monitor the safety and efficacy of vaccines in tens of thousands of people, or more, across many years.<ref name="NIH-site-2019" /><ref name=":who_vac_dev" />

=== Side effects ===
The US [[Centers for Disease Control and Prevention]] (CDC) has compiled a list of vaccines and their possible side effects.<ref name="USCDC-2018" />

=== Notable vaccine investigations ===
[[Dengvaxia]], the only approved vaccine for [[Dengue fever]], was found to increase the risk of hospitalization for Dengue fever by 1.58 times in children of 9 years or younger, resulting in the suspension of a mass vaccination program in the Philippines in 2017.<ref>{{cite journal | vauthors = Redoni M, Yacoub S, Rivino L, Giacobbe DR, Luzzati R, Di Bella S | title = Dengue: Status of current and under-development vaccines | journal = Reviews in Medical Virology | volume = 30 | issue = 4 | pages = e2101 | date = July 2020 | pmid = 32101634 | doi = 10.1002/rmv.2101 | hdl-access = free | s2cid = 211536962 | hdl = 1983/6d38d9b6-8e1b-4a84-85e3-edab4fc41957 | url = https://research-information.bris.ac.uk/en/publications/6d38d9b6-8e1b-4a84-85e3-edab4fc41957 | access-date = 23 September 2021 | archive-date = 20 March 2022 | archive-url = https://web.archive.org/web/20220320141819/https://research-information.bris.ac.uk/en/publications/dengue-status-of-current-and-under-development-vaccines | url-status = live }}</ref>

[[Pandemrix]] {{ndash}} a vaccine for the [[2009 swine flu pandemic vaccine|H1N1]] pandemic of 2009 given to around 31 million people<ref name="Chen-1998" /> {{ndash}} was found to have a higher level of adverse events than alternative vaccines resulting in legal action.<ref>{{cite journal | title = Pandemrix vaccine: why was the public not told of early warning signs? | journal = BMJ | volume = 362 | pages = k3948 | date = 20 September 2018 | pmid = 30237282 | doi = 10.1136/bmj.k3948 | s2cid = 52308748 | last1 = Doshi | first1 = Peter }}</ref> In a response to the [[narcolepsy]] reports following immunization with Pandemrix, the CDC carried out a population-based study and found the FDA-approved 2009 H1N1 flu shots were not associated with an increased risk for the neurological disorder.<ref>{{Cite web|url=https://www.cdc.gov/vaccinesafety/concerns/history/narcolepsy-flu.html|title=Narcolepsy Following Pandemrix in Europe|date=20 August 2020|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=3 January 2021|archive-date=27 June 2016|archive-url=https://web.archive.org/web/20160627180432/http://www.cdc.gov/vaccinesafety/concerns/history/narcolepsy-flu.html|url-status=live}}</ref>

=== Ingredients ===
The ingredients of vaccines can vary greatly from one to the next and no two vaccines are the same. The CDC has compiled a list of vaccines and their ingredients that is readily accessible on their website.<ref>{{Cite web|url=https://www.cdc.gov/vaccines/vac-gen/additives.htm|title=Vaccines: Vac-Gen/Additives in Vaccines Fact Sheet|date=12 July 2018|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=15 March 2019|archive-date=30 May 2019|archive-url=https://web.archive.org/web/20190530215608/https://www.cdc.gov/vaccines/vac-gen/additives.htm|url-status=live}}</ref>

==== Aluminium ====
[[Aluminium]] is an adjuvant ingredient in some vaccines. An adjuvant is a type of ingredient that is used to help the body's immune system create a stronger immune response after receiving the vaccination.<ref name="AdjuvantsUSCDC-2019a">{{Cite web|url=https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html|title=Adjuvants help vaccines work better. Vaccine Safety CDC|date=23 January 2019|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=15 March 2019|archive-date=15 March 2019|archive-url=https://web.archive.org/web/20190315224921/https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html|url-status=live}}</ref> Aluminium is in a [[Salt (chemistry)|salt]] form (the ionic version of an element) and is used in the following compounds: [[aluminium hydroxide]], [[aluminium phosphate]], and [[aluminium potassium sulfate]]. For a given element, the [[ion]] form has different properties from the elemental form. Although it is possible to have [[Aluminium toxicity in people on dialysis|aluminium toxicity]], [[aluminium salt]]s have been used effectively and safely since the 1930s when they were first used with the [[diphtheria]] and [[tetanus]] vaccines.<ref name="AdjuvantsUSCDC-2019a" /> Although there is a small increase in the chance of having a local reaction to a vaccine with an aluminium salt (redness, soreness, and swelling), there is no increased risk of any serious reactions.<ref>{{cite journal | vauthors = Jefferson T, Rudin M, Di Pietrantonj C | title = Adverse events after immunisation with aluminium-containing DTP vaccines: systematic review of the evidence | journal = The Lancet. Infectious Diseases | volume = 4 | issue = 2 | pages = 84–90 | date = February 2004 | pmid = 14871632 | doi = 10.1016/S1473-3099(04)00927-2 }}</ref><ref>{{cite journal | vauthors = Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO | title = Updated aluminum pharmacokinetics following infant exposures through diet and vaccination | journal = Vaccine | volume = 29 | issue = 51 | pages = 9538–43 | date = November 2011 | pmid = 22001122 | doi = 10.1016/j.vaccine.2011.09.124 | doi-access = free }}</ref>

==== Mercury ====
Certain vaccines once contained a compound called [[thiomersal]] or thimerosal, which is an [[organic compound]] containing [[Mercury (element)|mercury]]. [[Organomercury]] is commonly found in two forms. The [[methylmercury]] cation (with one carbon atom) is found in mercury-contaminated fish and is the form that people might ingest in mercury-polluted areas ([[Minamata disease]]), whereas the [[ethylmercury]] cation (with two carbon atoms) is present in thimerosal, linked to [[thiosalicylic acid|thiosalicylate]].<ref name="ThimerosalUSCDC-2019b">{{Cite web|url=https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html|title=Thimerosal in Vaccines Thimerosal Concerns Vaccine Safety CDC|date=24 January 2019|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=22 March 2019|archive-date=17 August 2011|archive-url=https://web.archive.org/web/20110817063316/http://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html|url-status=live}}</ref> Although both are organomercury compounds, they do not have the same chemical properties and interact with the human body differently. Ethylmercury is cleared from the body faster than methylmercury and is less likely to cause toxic effects.<ref name="ThimerosalUSCDC-2019b" />

Thimerosal was used as a [[preservative]] to prevent the growth of [[bacteria]] and [[Fungus|fungi]] in vials that contain more than one dose of a vaccine.<ref name="ThimerosalUSCDC-2019b" /> This helps reduce the risk of potential [[infection]]s or serious illness that could occur from [[contamination]] of a vaccine vial. Although there was a small increase in risk of injection site redness and swelling with vaccines containing thimerosal, there was no increased risk of serious harm or [[autism]].<ref>{{cite journal | vauthors = Ball LK, Ball R, Pratt RD | title = An assessment of thimerosal use in childhood vaccines | journal = Pediatrics | volume = 107 | issue = 5 | pages = 1147–54 | date = May 2001 | pmid = 11331700 | doi = 10.1542/peds.107.5.1147 }}</ref><ref>{{Cite web|url=https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228#bib|title=Vaccine Safety & Availability - Thimerosal and Vaccines|website=www.fda.gov|access-date=22 March 2019|archive-date=6 January 2013|archive-url=https://web.archive.org/web/20130106215029/https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228#bib|url-status=dead}}</ref> Even though evidence supports the safety and efficacy of thimerosal in vaccines, thimerosal was removed from childhood vaccines in the United States in 2001 as a precaution.<ref name="ThimerosalUSCDC-2019b" />

=== Monitoring ===

CDC Immunization Safety Office initiatives<ref name="cdc">{{Cite web|url=https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/index.html|title=Vaccine Safety Monitoring Monitoring Ensuring Safety Vaccine Safety CDC|date=12 December 2018|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=24 March 2019|archive-date=30 March 2019|archive-url=https://web.archive.org/web/20190330112053/https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/index.html|url-status=live}}</ref>

Vaccine Adverse Event Reporting System ([[Vaccine Adverse Event Reporting System|VAERS]])<ref>{{Cite web|url=https://vaers.hhs.gov/|title=Vaccine Adverse Event Reporting System (VAERS)|website=vaers.hhs.gov|access-date=24 March 2019|archive-date=17 March 2019|archive-url=https://web.archive.org/web/20190317025059/https://vaers.hhs.gov/|url-status=live}}</ref>
|Food and Drug Administration ([[Food and Drug Administration|FDA]]) Center for Biologics Evaluation and Research ([[Center for Biologics Evaluation and Research|CBER]])<ref>{{Cite web|url=https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cber/|title=About the Center for Biologics Evaluation and Research (CBER)|website=www.fda.gov|access-date=24 March 2019|date=7 February 2019|archive-date=9 May 2017|archive-url=https://web.archive.org/web/20170509063921/https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/|url-status=dead}}</ref>
|Immunization Action Coalition (IAC)<ref>{{Cite web|url=http://www.immunize.org/|title=Immunization Action Coalition (IAC): Vaccine Information for Health Care Professionals|website=www.immunize.org|access-date=24 March 2019|archive-date=14 December 2017|archive-url=https://web.archive.org/web/20171214105220/http://www.immunize.org/catg.d/p4209.pdf|url-status=live}}</ref>

Vaccine Safety Datalink ([[Vaccine Safety Datalink|VSD]])<ref>{{Cite web|url=https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.html|title=Vaccine Safety Datalink (VSD) VSD Monitoring Ensuring Safety Vaccine Safety CDC|date=10 January 2019|website=U.S. [[Centers for Disease Control and Prevention]] (CDC)|access-date=24 March 2019|archive-date=30 March 2019|archive-url=https://web.archive.org/web/20190330105907/https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.html|url-status=live}}</ref>
|Health Resources and Service Administration ([[Health Resources and Services Administration|HRSA]])<ref>{{Cite web|url=https://www.hrsa.gov/|title=Official web site of the U.S. Health Resources & Services Administration|website=www.hrsa.gov|access-date=24 March 2019|archive-date=23 March 2019|archive-url=https://web.archive.org/web/20190323220751/https://www.hrsa.gov/|url-status=live}}</ref>
|Institute for Safe Medication Practices (ISMP)<ref>{{Cite web|url=https://www.ismp.org/home|title=Home|website=Institute For Safe Medication Practices|access-date=24 March 2019|archive-date=20 March 2022|archive-url=https://web.archive.org/web/20220320141815/https://www.ismp.org/|url-status=live}}</ref>

Clinical Immunization Safety Assessment (CISA) Project
National Institutes of Health ([[National Institutes of Health|NIH]])<ref>{{Cite web|url=https://www.nih.gov/|title=National Institutes of Health (NIH)|website=National Institutes of Health (NIH)|access-date=24 March 2019|archive-date=2 October 2019|archive-url=https://web.archive.org/web/20191002092840/https://www.nih.gov/|url-status=live}}</ref>

National Vaccine Program Office ([[National Vaccine Program Office|NVPO]])<ref>{{Cite web|url=https://www.hhs.gov/nvpo/index.html|title=National Vaccine Program Office (NVPO)|date=30 March 2016|website=HHS.gov|access-date=24 March 2019|archive-date=24 March 2019|archive-url=https://web.archive.org/web/20190324210714/https://www.hhs.gov/nvpo/index.html|url-status=live}}</ref>

The administration protocols, efficacy, and adverse events of vaccines are monitored by organizations of the US federal government, including the [[Centers for Disease Control and Prevention]] and the [[Food and Drug Administration]].<ref name=cdc/> Independent agencies are constantly re-evaluating vaccine practices.<ref name=cdc/><ref name="canada">{{Cite web|url=https://www.canada.ca/en/public-health/services/immunization/vaccine-safety.html|title=Vaccine safety, surveillance and reporting|publisher=Government of Canada|date=22 April 2014|access-date=14 April 2020|archive-date=13 April 2020|archive-url=https://web.archive.org/web/20200413031419/https://www.canada.ca/en/public-health/services/immunization/vaccine-safety.html|url-status=live}}</ref> As with all medications, vaccine use is determined by [[public health]] research, surveillance, and reporting to governments and the public.<ref name=cdc/><ref name=canada/>