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{{Short description|Vaccines to prevent rabies in humans and animals}}
{{Use dmy dates|date=AugustNovember 20202022}}
{{Drugbox
| Verifiedfields = changed
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<!-- Clinical data -->
| tradename = RabAvertRabavert, Rabipur, Rabivax, Speeda, others
| Drugs.com = {{drugs.com|monograph|rabies_vaccine}}
| MedlinePlus = a607023
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| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Rabies vaccine, human diploid cell (Imovax Rabies) Use During Pregnancy | website=Drugs.com | date=22 November 2019 | url=https://www.drugs.com/pregnancy/rabies-vaccine-human-diploid-cell.html | access-date=29 December 2019}}</ref>
| pregnancy_category =
| routes_of_administration = [[Intramuscular]], [[intradermal]]▼
| ATC_prefix = J07▼
| ATC_suffix = BG01▼
| ATC_supplemental = {{ATC|J06|AA06}}▼
 
| legal_AU = S4
| legal_AU_comment = <ref name="TGA Verorab" />
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| legal_US = Rx-only
| legal_US_comment = <ref name="Imovax Rabies FDA label">{{cite web | title=Imovax Rabies (rabies virus strain pm-1503-3m antigen- propiolactone inactivated and water kit | website=DailyMed | date=21 October 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ba8d4e72-f452-4859-ae6f-3644b4b0a78c | access-date=2 November 2020}}</ref><ref name="Rabavert FDA label">{{cite web | title=Rabavert- rabies vaccine kit | website=DailyMed | date=18 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bd32ad4a-21b9-4890-9c37-4a6d1eff3145 | access-date=2 November 2020}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref name="EMA Rabies" />
| legal_status = Rx-only
▲| routes_of_administration = [[Intramuscular]], [[intradermal]]
▲| ATC_prefix = J07
▲| ATC_suffix = BG01
▲| ATC_supplemental = {{ATC|J06|AA06}}
 
<!-- Identifiers -->
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| UNII2 = C4HQF74XMW
| KEGG = D06504
 
<!-- Chemical data -->
}}
 
<!-- Definition and medical uses -->
The '''rabies vaccine''' is a [[vaccine]] used to prevent [[rabies]].<ref name=WHO2018>{{cite journal | vauthors = ((World Health Organization)) | title = Rabies vaccines: WHO position paper – April 2018 | journal = Weekly Epidemiological Record | date = 2018 | issue = 16 | volume = 93 | pages = 201–19 | hdl = 10665/272372 | hdl-access = free | author-link = World Health Organization |url=https://apps.who.int/iris/bitstream/handle/10665/272372/WER9316-201-219.pdf}}</ref> There are a number of rabies vaccines available that are both safe and effective.<ref name=WHO2018/> They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, which is commonly caused by a dog bite or a bat bite.<ref name=WHO2018/>
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<!--History, society and culture -->
The first rabies vaccine was introduced in 1885 and was followed by an improved version in 1908.<ref>{{cite book|last1=Nunnally|first1=Brian|title=Vaccine Analysis: Strategies, Principles, and Control|date=2014|publisher=Springer|isbn=9783662450246|page=63|url=https://books.google.com/books?id=vJKeBQAAQBAJ&pg=PA63|url-status=live|archive-url=https://web.archive.org/web/20160305091504/https://books.google.com/books?id=vJKeBQAAQBAJ&pg=PA63|archive-date=5 March 2016-03-05}}</ref> Millions of people globally are vaccinated against the virus.<ref name=WHO2018/> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>
 
==Medical uses==
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===After exposure===
For individuals who have been potentially exposed to the virus, four doses over two weeks are recommended, as well as an injection of [[rabies immunoglobulin]] with the first dose.<ref>{{cite web |title=Rabies Vaccine Information Statement |url=https://www.cdc.gov/vaccines/hcp/vis/vis-statements/rabies.html |access-date=27 September 2019 |date=6 October 2009-10-06 |website=[[Centers for Disease Control and Prevention]] (CDC)}}</ref> This is known as post-exposure vaccination.<ref name="J"/> For people who have previously been vaccinated, only a single dose of the rabies vaccine is required.<ref name="J"/> However, vaccination after exposure is neither a treatment nor a cure for rabies; it can only prevent the development of rabies in a person if given before the virus reaches the brain.<ref name="J">{{cite web|url=https://www.cdc.gov/rabies/medical_care/index.html|title=Rabies Postexposure Prophylaxis (PEP)|website=[[Centers for Disease Control and Prevention]] (CDC)|date= 11 June 2019|access-date=19 November 2019}}</ref> Because the rabies virus has a relatively long incubation period, post-exposure vaccinations are typically highly effective.<ref name=WHO2018 />
 
=== Additional doses ===
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The vaccine was attenuated and prepared in the H.D.C. strain [[WI-38]] which was gifted to Dr. Hilary Koprowski at the Wistar Institute by Dr. [[Leonard Hayflick]], an Associate Member, who developed this normal human diploid cell strain.<ref>{{cite journal |last1=Hayflick |first1=L. |last2=Moorhead |first2=P.S. |title=The serial cultivation of human diploid cell strains |journal=Experimental Cell Research |date=December 1961 |volume=25 |issue=3 |pages=585–621 |doi=10.1016/0014-4827(61)90192-6|pmid=13905658 }}</ref><ref>{{cite journal |last1=Hayflick |first1=L. |title=The limited in vitro lifetime of human diploid cell strains |journal=Experimental Cell Research |date=March 1965 |volume=37 |issue=3 |pages=614–636 |doi=10.1016/0014-4827(65)90211-9|pmid=14315085 }}</ref>
 
Verorab, developed by [[Sanofi-Aventis]], is a mammalian [[vero cell]] based rabies vaccine approved by the [[World Health Organization]].<ref>{{cite web | title=Verorab | website=[[World Health Organization]] (WHO | date=22 June 2005 | url=https://extranet.who.int/pqweb/content/verorab | access-date=23 November 2022}}</ref><ref name="Toovey 2007 pp. 327–348">{{cite journal | vauthors = Toovey S | title = Preventing rabies with the Verorab vaccine: 1985-2005 Twenty years of clinical experience | journal = Travel Medicine and Infectious Disease | volume = 5 | issue = 6 | pages = 327–48 | date = November 2007 | pmid = 17983973 | doi = 10.1016/j.tmaid.2007.07.004 }}</ref> It is approved for medical use in Australia and the European countriesUnion and is [[indicated]] for both pre-exposure and post-exposure prophylaxis against rabies.<ref name="TGA Verorab">{{cite web|url=https://www.tga.gov.au/resources/prescription-medicines-registrations/verorab-sanofi-aventis-australia-pty-ltd|title=Verorab|access-date=23 November 2022-11-23|date=2022-10-28 October 2022|publisher=[[Therapeutic Goods Administration]] (TGA) }}</ref><ref name="EMA Rabies">{{cite web|url=https://www.ema.europa.eu/en/documents/psusa/rabies-vaccine-list-nationally-authorised-medicinal-products-psusa/00009277/202103_en.pdf|publisher=[[European Medicines Agency]] (EMA) |access-date=2022-11-23 November 2022|date=2021-10-21 October 2021|title=List of nationally authorised medicinal products, Active substance: rabies vaccine, Procedure no.: PSUSA/00009277/202103}}</ref>
 
==History==
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Virtually all infections with rabies resulted in death until two French scientists, [[Louis Pasteur]] and [[Émile Roux]], developed the first rabies vaccination in 1885. Nine-year-old [[Joseph Meister]] (1876–1940), who had been mauled by a rabid dog, was the first human to receive this vaccine.<ref>{{cite journal |doi=10.2307/3560403 |author=Geison GL |title=Pasteur's work on rabies: Reexamining the ethical issues diagnosis for developing countries |journal=Hastings Center Report |issue=April |pages=26– |year=1978 |jstor=3560403 |volume=8 |publisher=The Hastings Center |pmid=348641}}</ref> The treatment started with a [[subcutaneous injection]] on 6 July 1885, at 8:00{{nbsp}}pm, which was followed with 12 additional doses administered over the following 10 days. The first injection was derived from the spinal cord of an inoculated rabbit which had died of rabies 15 days earlier. All the doses were obtained by [[Attenuated vaccine|attenuation]], but later ones were progressively more virulent.<ref>{{cite journal|title=Four Thousand Years of Concepts Relating to Rabies in Animals and Humans, Its Prevention and Its Cure| author=Arnaud Tarantola | year=2017 | doi=10.3390/tropicalmed2020005 | pmid=30270864 | pmc=6082082 | journal=Trop Med Infect Dis | volume= 2| issue=2 | pages=5 | doi-access=free }}</ref>
 
The Pasteur-Roux vaccine attenuated the harvested virus samples by allowing them to dry for five to ten days. Similar nerve tissue-derived vaccines are still used in some countries, and while they are much cheaper than modern cell culture vaccines, they are not as effective.<ref name=Plotkin1980>{{cite journal|author = Plotkin, Stanley A.|title = Rabies Vaccine Prepared in Human Cell Cultures: Progress and Perspectives|journal = Reviews of Infectious Diseases|volume = 2|issue =3|pages = 433–448|year = 1980|doi = 10.1093/clinids/2.3.433|pmid = 6158081}}</ref> Neural tissue vaccines also carry a certain risk of neurological complications.<ref name="pmid15069272">{{cite journal |last1=Srivastava|first1= AK|last2=Sardana|first2= V|last3=Prasad|first3= K|last4=Behari|first4= M |title=Diagnostic dilemma in flaccid paralysis following anti-rabies vaccine |journal=Neurol India |volume=52 |issue=1 |pages=132–3 |date=March 2004 |pmid=15069272 |url=http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2004;volume=52;issue=1;spage=132;epage=133;aulast=Srivastava |url-status=live |archive-url=https://web.archive.org/web/20090802195908/http://www.neurologyindia.com/article.asp?issn=0028-3886%3Byear%3D2004%3Bvolume%3D52%3Bissue%3D1%3Bspage%3D132%3Bepage%3D133%3Baulast%3DSrivastava |archive-date=2 August 2009-08-02 }}</ref>
 
== Society and culture ==
==Cost==
=== Economics ===
 
When the modern cell-culture rabies vaccine was first introduced in the early 1980s, it cost $45 per dose, and was considered to be too expensive. The cost of the rabies vaccine continues to be a limitation to acquiring pre-exposure rabies immunization for travelers from developed countries. In 2015, in the United States, a course of three doses could cost over {{US$|1,000}}, while in Europe a course costs around €100{{Euro|100}}. It is possible and more cost-effective to split one intramuscular dose of the vaccine into several intradermal doses. This method is recommended by the [[World Health OrganisationOrganization]] (WHO) in areas that are constrained by cost or with supply issues. The route is as safe and effective as intramuscular according to the WHO.<ref>{{cite web |title=Vaccinations and immunization Rabies |url=https://www.who.int/teams/control-of-neglected-tropical-diseases/rabies/vaccinations-and-immunization |website=[[World Health Organization]] (WHO) |language=en}}</ref>
 
==Veterinary use==
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[[File:Lysvulpen.jpg|thumb|Baits with vaccine for oral vaccination]]
[[File:Oral vaccination.jpg|thumb|Machine for distribution of baits from airplane]]
Pre-exposure [[immunization]] has been used on domesticated and wild populations. In many jurisdictions, domestic dogs, cats, ferrets, and rabbits are required to be vaccinated.<ref>{{Cite web|url=http://lawatlas.org/datasets/rabies-vaccination-laws|title=State Rabies Vaccination Laws for Domestic Dogs, Cats, and Ferrets in the United States|website=lawatlas.org|access-date=2020-01-22 January 2020}}</ref>
 
There are two main types of vaccines used for domesticated animals and pets (including pets from wildlife species):
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===Dogs===
Aside from vaccinating humans, another approach was also developed by vaccinating dogs to prevent the spread of the virus. In 1979, the Van Houweling Research Laboratory of the [[Silliman University]] Medical Center in [[Dumaguete]] in the [[Philippines]]<ref>[http://www.worldrabiesday.org/EN/Media_Center/Perspectives.html "Dr. George W. Beran's Biography"] {{webarchive |url=https://web.archive.org/web/20100415205245/http://www.worldrabiesday.org/EN/Media_Center/Perspectives.html |date=15 April 2010 }}. World Rabies Day. Retrieved 2010-04-23 April 2010.</ref> developed and produced a [[dog vaccine]] that gave a three-year immunity from [[rabies]]. The development of the vaccine resulted in the elimination of rabies in many parts of the [[Visayas]] and [[Mindanao]] Islands. The successful program in the Philippines was later used as a model by other countries, such as [[Ecuador]] and the [[Yucatan|Yucatan State]] of Mexico, in their fight against rabies conducted in collaboration with the [[World Health Organization]].<ref>[http://www.onehealthinitiative.com/publications/RabiesPresentationWithNotes1.pdf "One World, One Health Rabies"] {{webarchive|url=https://web.archive.org/web/20110724035935/http://www.onehealthinitiative.com/publications/RabiesPresentationWithNotes1.pdf |date=2011-07-24 July 2011 }}.OneHealthInitiative.com. Retrieved 2010-04-23 April 2010.</ref>
 
In [[Tunisia]], a rabies control program was initiated to give dog owners free vaccination to promote mass vaccination which was sponsored by their government. The vaccine is known as Rabisin ([[Merial|Mérial]]), which is a [[Cell (biology)|cell]] based rabies vaccine only used countrywide. Vaccinations are often administered when owners take in their dogs for check-ups and visits at the vet.<ref>{{cite journal|title = Evaluation of Mass Vaccination Campaign Coverage Against Rabies in Dogs in Tunisia|journal = Zoonoses and Public Health|volume = 58|issue = 2|pages = 110–8|date = 23 DecDecember 2009|publisher = Institut Pasteur de Tunis and Blackwell Verlag GmbH|doi = 10.1111/j.1863-2378.2009.01306.x|pmid = 20042063|last1 = Touihri|last2 = Zaouia|first2 = I.|last3 = Elhili|first3 = K.|last4 = Dellagi|first4 = K.|last5 = Bahloul|first5 = C.|s2cid = 232553}}</ref>
 
Oral rabies vaccines (see below for details) have been trialled on feral/stray dogs in some areas with high rabies incidence, as it could potentially be more efficient than catching and injecting them. However these have not been deployed for dogs at large scale yet.<ref>{{cite journal
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==== Oral rabies vaccine ====
Oral rabies vaccines in pellet form are intended to be given to wild animals to produce a [[herd immunity]] effect.<ref>{{cite web|title = What are the signs and symptoms of rabies?|url = https://www.cdc.gov/rabies/symptoms/|website = [[Centers for Disease Control and Prevention]] (CDC)|access-date = 9 November 2015-11-09|url-status = live|archive-url = https://web.archive.org/web/20151109135949/http://www.cdc.gov/rabies/symptoms/|archive-date = 9 November 2015-11-09}}</ref> The development of safe and effective rabies virus vaccines applied in attractive [[Bait (luring substance)|bait]]s resulted in the first field trials in Switzerland in 1978 to immunize red foxes.<ref>{{cite journal | pmid = 15742629 | volume=119 | title=Oral vaccination of wildlife against rabies: opportunities and challenges in prevention and control |vauthors=Rupprecht CE, Hanlon CA, Slate D | journal=Dev Biol | pages=173–84| year=2004 }}</ref>
 
There are currently two different types of oral wildlife rabies vaccine in use:
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Oral rabies vaccination (ORV) programs have been used in many countries in an effort to control the spread of rabies and limit the risk of human contact with the rabies virus.<ref name="A" /> ORV programs were initiated in Europe in the 1980s, Canada in 1985, and in the United States in 1990.<ref name="C2" /> ORV is a preventive measure to eradicate [[rabies]] in wild animal vectors of disease, mainly [[fox]]es, [[raccoon]]s, [[raccoon dog]]s, [[coyote]]s and [[jackal]]s, but also can be used for [[dog]]s in [[developing countries]].<ref>{{cite web|url=http://www.rabies-vaccination.com/oral-vaccination.asp |title=Oral rabies vaccination |access-date=21 February 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140107053303/http://www.rabies-vaccination.com/oral-vaccination.asp |archive-date=7 January 2014 }}</ref> ORV programs typically use edible baits to deliver the vaccine to targeted animals. ORV baits consist of a small packet containing the oral vaccine which is then either coated in a fishmeal paste or encased in a fishmeal-polymer block.<ref name="A" /> When an animal bites into the bait, the packets burst and the vaccine is administered.<ref name="C2">{{Cite web|url=https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_rabies_vaccine_info|title=Oral Rabies Vaccine Information|date=12 November 2019|website=[[Animal and Plant Health Inspection Service]] (APHIS)}}</ref> Current research suggests that if adequate amounts of the vaccine is ingested, immunity to the virus should last for upwards of one year.<ref name="F">{{Cite web|url=https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_rabies_faqs|title=Frequently Asked Questions|date=12 November 2019|website=[[Animal and Plant Health Inspection Service]] (APHIS)}}</ref> By immunizing wild or stray animals, ORV programs work to create a buffer zone between the rabies virus and potential contact with humans, pets, or livestock.<ref name="C2" /> The effectiveness of ORV campaigns in specific areas is determined through trap-and-release methods.<ref name="I">{{cite web|url=https://www.aphis.usda.gov/publications/wildlife_damage/content/printable_version/fs_oral_rabies_2011.pdf|title=Oral Rabies Vaccination Program in the East|date=January 2011|website=[[Animal and Plant Health Inspection Service]] (APHIS)|access-date=19 November 2019|archive-date=11 February 2017|archive-url=https://web.archive.org/web/20170211021102/https://www.aphis.usda.gov/publications/wildlife_damage/content/printable_version/fs_oral_rabies_2011.pdf|url-status=dead}}</ref> Titer tests are performed on the blood drawn from the sample animals in order to measure rabies antibody levels in the blood.<ref name="I" /> Baits are usually distributed by aircraft to more efficiently cover large, rural regions. In order to place baits more precisely and to minimize human and pet contact with baits, however, they are distributed by hand in suburban or urban regions.<ref name="C2" />
 
ORV programs have seen success in preventing the westward spread of raccoon variant rabies in the United States and even eradicating rabies in red foxes in Switzerland.<ref>{{Cite web|url=http://www.vdh.virginia.gov/environmental-epidemiology/rabies-control/oral-rabies-vaccine-project/|title=Oral Rabies Vaccine Project – Environmental Epidemiology|website=www.vdh.virginia.gov|access-date=2017-07-23 July 2017|url-status=live|archive-url=https://web.archive.org/web/20170818031909/http://www.vdh.virginia.gov/environmental-epidemiology/rabies-control/oral-rabies-vaccine-project/|archive-date=2017-08-18 August 2017}}</ref><ref>{{Cite web|url=http://nowiknow.com/switzerlands-kind-of-gross-incredibly-effective-anti-rabies-weapon/|title=Switzerland's Kind of Gross, Incredibly Effective Anti-Rabies Weapon {{!}} Now I Know|website=nowiknow.com|access-date=2017-07-23 July 2017|url-status=live|archive-url=https://web.archive.org/web/20160212072458/http://nowiknow.com/switzerlands-kind-of-gross-incredibly-effective-anti-rabies-weapon/|archive-date=2016-02-12 February 2016}}</ref>
 
The oral vaccine does not contain the whole rabies virus and has been proven safe in over 60 animal species including cats and dogs.<ref name="F" /> The idea of [[wildlife]] vaccination was conceived during the 1960s, and modified-live rabies viruses were used for the experimental oral vaccination of [[carnivores]] by the 1970s. The potential for human contact with baits is a present concern for ORV programs, but the inactivated rabies vaccine cannot cause rabies, and the recombinant poxvirus vaccine is based on an attenuated poxvirus which is unlikely to cause serious disease in humans anyway. In the USA between 1990 and 2000, over 22 million doses of vaccinia-rabies were distributed, but there were only 160 incidents of people touching a vaccine bait, and only one resulted in a serious infection. The person in this case had been bitten by her dog while removing a bait from its mouth.<ref>{{cite journal
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| pages =582–586
| date =August 23, August 2001
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| url =https://www.nejm.org/doi/full/10.1056/NEJMoa010560
| jstor =
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