Rabies vaccine#History

The World Health Organization (WHO) recommends vaccinating those who are at high risk of the disease, such as children who live in areas where it is common. Other groups may include veterinarians, researchers, or people planning to travel to regions where rabies is common. Three doses of the vaccine are given over a one-month period on days zero, seven, and either twenty-one or twenty-eight.{{cite web|url=https://www.cdc.gov/rabies/specific_groups/travelers/pre-exposure_vaccinations.html|title=Preexposure Vaccinations|website=Centers for Disease Control and Prevention (CDC)|date=22 April 2011|access-date=19 November 2019|archive-date=23 August 2019|archive-url=https://web.archive.org/web/20190823204408/https://www.cdc.gov/rabies/specific_groups/travelers/pre-exposure_vaccinations.html|url-status=live}}

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.{{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=June 2022 |website=U.S. Centers for Disease Control and Prevention (CDC) |archive-date=6 November 2019 |archive-url=https://web.archive.org/web/20191106204753/https://www.cdc.gov/vaccines/hcp/vis/vis-statements/rabies.html |url-status=live }} This is known as post-exposure vaccination. For people who have previously been vaccinated, only a single dose of the rabies vaccine is required. 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.{{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=16 November 2019|access-date=19 November 2019|archive-date=21 December 2019|archive-url=https://web.archive.org/web/20191221185807/https://www.cdc.gov/rabies/medical_care/index.html|url-status=live}} Because the rabies virus has a relatively long incubation period, post-exposure vaccinations are typically highly effective.

Immunity following a course of doses is typically long lasting, and additional doses are usually not needed unless the person has a high risk of contracting the virus. Those at risk may have tests done to measure the amount of rabies antibodies in the blood, and then get rabies boosters as needed. Following administration of a booster dose, one study found 97% of immunocompetent individuals demonstrated protective levels of neutralizing antibodies after ten years.{{cite journal | vauthors = | title = An Advisory Committee Statement (ACS). Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on travellers and rabies vaccine | journal = Canada Communicable Disease Report | volume = 28 | issue = ACS-4 | pages = 1–12 | date = March 2002 | pmid = 11889905 | url = http://publications.gc.ca/collections/Collection/H12-21-2-28-4.pdf | access-date = 7 January 2020 | url-status = live | archive-url = https://web.archive.org/web/20200831223415/http://publications.gc.ca/collections/Collection/H12-21-2-28-4.pdf | archive-date = 31 August 2020 }}

Rabies vaccines are safe in all age groups.{{cite web|url=https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_national_rabies_management_program_overview|title=National Rabies Management Program Overview|website=Animal and Plant Health Inspection Service (APHIS)|access-date=12 November 2019|archive-date=3 August 2020|archive-url=https://web.archive.org/web/20200803093734/https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/CT_National_Rabies_Management_Program_Overview|url-status=live}} About 35 to 45 percent of people develop a brief period of redness and pain at the injection site, and 5 to 15 percent of people may experience fever, headaches, or nausea. Because of the certain fatality of the virus, receiving the vaccine is always advisable.

Vaccines made from nerve tissue are used in a few countries, mainly in Asia and Latin America, but are less effective and have greater side effects. Their use is thus not recommended by the World Health Organization.

The human diploid cell rabies vaccine (HDCV) was started in 1967. Human diploid cell rabies vaccines are inactivated vaccines made using the attenuated Pitman-Moore L503 strain of the virus.{{cite web|title=Rabies - Human Vaccines|url=https://www.who.int/rabies/vaccines/human_vaccines/en/index.html|publisher=World Health Organization (WHO)|access-date=1 October 2012|url-status=dead|archive-url=https://web.archive.org/web/20121103135631/http://www.who.int/rabies/vaccines/human_vaccines/en/index.html|archive-date=3 November 2012}}

In addition to these developments, newer and less expensive purified chicken embryo cell vaccines (CCEEV) and purified Vero cell rabies vaccines are now available and are recommended for use by the WHO. The purified Vero cell rabies vaccine uses the attenuated Wistar strain of the rabies virus, and uses the Vero cell line as its host. CCEEVs can be used in both pre- and post-exposure vaccinations. CCEEVs use inactivated rabies virus grown from either embryonated eggs or in cell cultures and are safe for use in humans and animals.{{cite web|url=https://www.who.int/ith/vaccines/rabies/en/|title=Rabies|website=World Health Organization (WHO)|access-date=21 November 2019|archive-date=15 February 2015|archive-url=https://web.archive.org/web/20150215014809/http://www.who.int/ith/vaccines/rabies/en/|url-status=live}}

The vaccine was attenuated and prepared in the H.D.C. strain WI-38 which was gifted to Hilary Koprowski at the Wistar Institute by Leonard Hayflick, an Associate Member, who developed this normal human diploid cell strain.{{cite journal | vauthors = Hayflick L, Moorhead PS | title = The serial cultivation of human diploid cell strains | journal = Experimental Cell Research | volume = 25 | issue = 3 | pages = 585–621 | date = December 1961 | pmid = 13905658 | doi = 10.1016/0014-4827(61)90192-6 }}{{cite journal | vauthors = Hayflick L | title = The limited in vitro lifetime of human diploid cell strains | journal = Experimental Cell Research | volume = 37 | issue = 3 | pages = 614–636 | date = March 1965 | pmid = 14315085 | doi = 10.1016/0014-4827(65)90211-9 }}

Verorab, developed by Sanofi-Aventis and Speeda, developed by Liaoning Chengda are purified vero cell rabies vaccine (PVRV).{{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 = 327–348 | date = November 2007 | pmid = 17983973 | doi = 10.1016/j.tmaid.2007.07.004 }}{{cite journal | vauthors = Yu P, Huang Y, Zhang Y, Tang Q, Liang G | title = Production and evaluation of a chromatographically purified Vero cell rabies vaccine (PVRV) in China using microcarrier technology | journal = Human Vaccines & Immunotherapeutics | volume = 8 | issue = 9 | pages = 1230–1235 | date = September 2012 | pmid = 22894963 | pmc = 3579903 | doi = 10.4161/hv.20985 }} The first is approved by the World Health Organization.{{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 | archive-date=24 November 2022 | archive-url=https://web.archive.org/web/20221124032320/https://extranet.who.int/pqweb/content/verorab | url-status=live }} Verorab is approved for medical use in Australia and the European Union and is indicated for both pre-exposure and post-exposure prophylaxis against rabies.{{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|date=28 October 2022|publisher=Therapeutic Goods Administration (TGA)|archive-date=22 November 2022|archive-url=https://web.archive.org/web/20221122020146/https://www.tga.gov.au/resources/prescription-medicines-registrations/verorab-sanofi-aventis-australia-pty-ltd|url-status=live}}{{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=23 November 2022|date=21 October 2021|title=List of nationally authorised medicinal products, Active substance: rabies vaccine, Procedure no.: PSUSA/00009277/202103|archive-date=1 February 2023|archive-url=https://web.archive.org/web/20230201180643/https://www.ema.europa.eu/en/documents/psusa/rabies-vaccine-list-nationally-authorised-medicinal-products-psusa/00009277/202103_en.pdf|url-status=live}}

Image:Aplicação de vacina anti-rábica.jpg, Brazil]]

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.{{cite journal | vauthors = Geison GL | title = Pasteur's work on rabies: reexamining the ethical issues | journal = The Hastings Center Report | volume = 8 | issue = 2 | pages = 26–33 | date = April 1978 | pmid = 348641 | doi = 10.2307/3560403 | publisher = The Hastings Center | jstor = 3560403 }} 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 attenuation, but later ones were progressively more virulent.{{cite journal | vauthors = Tarantola A | title = Four Thousand Years of Concepts Relating to Rabies in Animals and Humans, Its Prevention and Its Cure | journal = Tropical Medicine and Infectious Disease | volume = 2 | issue = 2 | pages = 5 | date = March 2017 | pmid = 30270864 | pmc = 6082082 | doi = 10.3390/tropicalmed2020005 | doi-access = free }}

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.{{cite journal | vauthors = Plotkin SA | 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 | pmid = 6158081 | doi = 10.1093/clinids/2.3.433 }} Neural tissue vaccines also carry a certain risk of neurological complications.{{cite journal | vauthors = Srivastava AK, Sardana V, Prasad K, Behari M | title = Diagnostic dilemma in flaccid paralysis following anti-rabies vaccine | journal = Neurology India | volume = 52 | issue = 1 | pages = 132–133 | 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 }}

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 {{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 Organization (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.{{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) |access-date=25 November 2022 |archive-date=28 September 2022 |archive-url=https://web.archive.org/web/20220928191059/https://www.who.int/teams/control-of-neglected-tropical-diseases/rabies/vaccinations-and-immunization |url-status=live }}

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File:Oral vaccination.jpg

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.{{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=22 January 2020|archive-date=22 January 2020|archive-url=https://web.archive.org/web/20200122005149/http://lawatlas.org/datasets/rabies-vaccination-laws|url-status=live}}

There are two main types of vaccines used for domesticated animals and pets (including pets from wildlife species):

• Inactivated rabies virus (similar technology to that given to humans) administered by injection
• Modified live viruses administered orally (by mouth): Live rabies virus from attenuated strains. Attenuated means strains that have developed mutations that cause them to be weaker and do not cause disease.{{cite book | title =OIE Terrestrial Manual | publisher =World Organisation for Animal Health | year =2018 | chapter =3.1.17 Rabies (Infection with Rabies Virus and Other Lyssaviruses) | chapter-url =https://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/3.01.17_RABIES.pdf | access-date =22 July 2021 | archive-date =3 July 2021 | archive-url =https://web.archive.org/web/20210703025740/https://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/3.01.17_RABIES.pdf | url-status =live }}

Imrab is an example of a veterinary rabies vaccine containing the Pasteur strain of killed rabies virus. Several different types of Imrab exist, including Imrab, Imrab 3, and Imrab Large Animal. Imrab 3 has been approved for ferrets and, in some areas, pet skunks.{{cite web|url=http://us.merial.com/equine/products/equine_imrab3.asp|title=Imrab 3|archive-url=https://web.archive.org/web/20050409033141/http://us.merial.com/equine/products/equine_imrab3.asp |archive-date=9 April 2005|url-status=dead|publisher=Merial }}

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{{cite web|url-status=dead|url=http://www.worldrabiesday.org/EN/Media_Center/Perspectives.html|title=Dr. George W. Beran's Biography|archive-url=https://web.archive.org/web/20100415205245/http://www.worldrabiesday.org/EN/Media_Center/Perspectives.html |archive-date=15 April 2010|publisher=World Rabies Day|access-date=23 April 2010}} 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 Mexican state of Yucatán, in their fight against rabies conducted in collaboration with the World Health Organization.{{cite web|url=http://www.onehealthinitiative.com/publications/RabiesPresentationWithNotes1.pdf|title=One World, One Health Rabies|archive-url=https://web.archive.org/web/20110724035935/http://www.onehealthinitiative.com/publications/RabiesPresentationWithNotes1.pdf |archive-date=24 July 2011|url-status=dead|website=OneHealthInitiative.com|access-date=23 April 2010| vauthors = Beran GW }}

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 (Mérial), which is a 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.{{cite journal | vauthors = Touihri L, Zaouia I, Elhili K, Dellagi K, Bahloul C | title = Evaluation of mass vaccination campaign coverage against rabies in dogs in Tunisia | journal = Zoonoses and Public Health | volume = 58 | issue = 2 | pages = 110–118 | date = March 2011 | pmid = 20042063 | doi = 10.1111/j.1863-2378.2009.01306.x | publisher = Institut Pasteur de Tunis and Blackwell Verlag GmbH | s2cid = 232553 }}

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.{{cite web | title = Oral vaccination of dogs against rabies: guidance for research on oral rabies vaccines and Field application of oral vaccination of dogs against rabies | publisher = World Health Organization | location = Geneva, Switzerland | date = 2007 | hdl = 10665/331036 | url = https://apps.who.int/iris/handle/10665/331036 | access-date = 25 November 2022 | archive-date = 25 November 2022 | archive-url = https://web.archive.org/web/20221125011757/https://apps.who.int/iris/handle/10665/331036 | url-status = live | last1 = Organization | first1 = World Health }}

Wildlife species, primarily bats, raccoons, skunks, and foxes, act as reservoir species for different variants of the rabies virus in distinct geographic regions of the United States.{{cite web |title=Oral Rabies Vaccination |url=https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nwrc/research-areas/SA_Rabies/CT_Orv_vaccination |url-status=dead |archive-url=https://web.archive.org/web/20200708025246/https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nwrc/research-areas/SA_Rabies/CT_Orv_vaccination |archive-date=8 July 2020 |access-date=12 November 2019 |website=Animal and Plant Health Inspection Service (APHIS)}}{{cite journal | vauthors = Gilbert AT | title = Rabies virus vectors and reservoir species | journal = Revue Scientifique et Technique | volume = 37 | issue = 2 | pages = 371–384 | date = August 2018 | pmid = 30747141 | doi = 10.20506/rst.37.2.2808 | s2cid = 73436726 | doi-access = free }} This results in the general occurrence of rabies as well as outbreaks in animal populations. Approximately 90% of all reported rabies cases in the US are from wildlife.

Oral rabies vaccines are distributed across the landscape, targeting reservoir species, in an effort to produce a herd immunity effect.{{cite book | vauthors = Chipman RB, Gilbert AT, Slate D | series = Fascinating Life Sciences | chapter = Wildlife Rabies Management in the New World: Prevention, Control and Elimination in Mesocarnivores |date=2023 | title = History of Rabies in the Americas: From the Pre-Columbian to the Present, Volume I |pages=143–198 | veditors = Rupprecht CE|place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-031-25052-1_7 |isbn=978-3-031-25051-4 }} 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.{{cite journal | vauthors = Baer GM | title = Rabies--an historical perspective | journal = Infectious Agents and Disease | volume = 3 | issue = 4 | pages = 168–180 | date = August 1994 | pmid = 7827785 | url = https://pubmed.ncbi.nlm.nih.gov/7827785/ | access-date = 14 November 2023 | archive-date = 8 November 2023 | archive-url = https://web.archive.org/web/20231108141632/https://pubmed.ncbi.nlm.nih.gov/7827785/ | url-status = live }} Development of an oral immunization for wildlife began in the United States with laboratory trials using the live, attenuated Evelyn-Rokitnicki-Abelseth (ERA) vaccine, derived from the Street Alabama Dufferin (SAD) strain.{{cite journal | vauthors = Maki J, Guiot AL, Aubert M, Brochier B, Cliquet F, Hanlon CA, King R, Oertli EH, Rupprecht CE, Schumacher C, Slate D, Yakobson B, Wohlers A, Lankau EW | display-authors = 6 | title = Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG^®): a global review | journal = Veterinary Research | volume = 48 | issue = 1 | pages = 57 | date = September 2017 | pmid = 28938920 | pmc = 5610451 | doi = 10.1186/s13567-017-0459-9 | doi-access = free }} The first ORV field trial using the live attenuated vaccine to immunize foxes occurred in Switzerland during 1978.{{cite journal | vauthors = Rupprecht CE, Hanlon CA, Slate D | title = Oral vaccination of wildlife against rabies: opportunities and challenges in prevention and control | journal = Developments in Biologicals | volume = 119 | pages = 173–184 | year = 2004 | pmid = 15742629 }}{{cite journal | vauthors = Winkler WG, Bögel K | title = Control of rabies in wildlife | journal = Scientific American | volume = 266 | issue = 6 | pages = 86–92 | date = June 1992 | pmid = 1585150 | doi = 10.1038/scientificamerican0692-86 | bibcode = 1992SciAm.266f..86W }}

There are currently three different types of oral wildlife rabies vaccine in use:

• Modified live virus: Attenuated vaccine strains of rabies virus such as SAG2 and SAD B19 {{cite web | title = Field application of oral rabies vaccines for dogs | work = Report of a WHO Consultation organized in collaboration with the Office International des Epizooties (OIE)| publisher = World Health Organization | location = Geneva, Switzerland | url = https://www.who.int/rabies/en/Field_application_for_oral_rabies_vaccines_for_dogs.pdf | archive-url = https://web.archive.org/web/20061014075630/https://www.who.int/rabies/en/Field_application_for_oral_rabies_vaccines_for_dogs.pdf | archive-date = 14 October 2006 | date = July 1998 }}
• Recombinant vaccinia virus expressing rabies glycoprotein (V-RG): This is a strain of the vaccinia virus (originally a smallpox vaccine) that has been engineered to encode the gene for the rabies glycoprotein.
• V-RG has been proven safe in over 60 animal species including cats and dogs.{{Cite web |date=12 November 2019 |title=Frequently Asked Questions |url=https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_rabies_faqs |url-status=live |archive-url=https://web.archive.org/web/20200817200000/https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_rabies_faqs |archive-date=17 August 2020 |access-date=19 November 2019 |website=Animal and Plant Health Inspection Service (APHIS)}} 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.
• ONRAB: an experimental live recombinant adenovirus vaccine {{cite journal | vauthors = Tordo N, Foumier A, Jallet C, Szelechowski M, Klonjkowski B, Eloit M | title = Canine adenovirus based rabies vaccines | journal = Developments in Biologicals | volume = 131 | pages = 467–476 | year = 2008 | pmid = 18634509 | url = https://pubmed.ncbi.nlm.nih.gov/18634509/ | url-status = live | access-date = 2023-01-29 | archive-url = https://web.archive.org/web/20230129193641/https://pubmed.ncbi.nlm.nih.gov/18634509/ | archive-date = 29 January 2023 }}{{cite journal | vauthors = Fehlner-Gardiner C, Rudd R, Donovan D, Slate D, Kempf L, Badcock J | title = Comparing ONRAB® AND RABORAL V-RG® oral rabies vaccine field performance in raccoons and striped skunks, New Brunswick, Canada, and Maine, USA | journal = Journal of Wildlife Diseases | volume = 48 | issue = 1 | pages = 157–167 | date = January 2012 | pmid = 22247384 | doi = 10.7589/0090-3558-48.1.157 | s2cid = 22571547 }}

Other oral rabies experimental vaccines in development include recombinant adenovirus vaccines.{{cite journal | vauthors = Tordo N, Foumier A, Jallet C, Szelechowski M, Klonjkowski B, Eloit M | title = Canine adenovirus based rabies vaccines | journal = Developments in Biologicals | volume = 131 | pages = 467–476 | year = 2008 | pmid = 18634509 | url = https://pubmed.ncbi.nlm.nih.gov/18634509/ | access-date = 2023-01-29 | url-status = live | archive-url = https://web.archive.org/web/20230129193641/https://pubmed.ncbi.nlm.nih.gov/18634509/ | archive-date = 29 January 2023 }}

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. ORV programs were initiated in Europe in the 1980s, Canada in 1985, and in the United States in 1990. ORV is a preventive measure to eliminate rabies in wild animal vectors of disease, mainly foxes, raccoons, raccoon dogs, coyotes and jackals, but also can be used for dogs in developing countries.{{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 }} ORV programs typically attractive baits to deliver the vaccine to targeted animals. In the United States, RABORAL V-RG (Boehringer Ingelheim, Duluth, GA, USA) has been the only licensed ORV for rabies virus management since 1997. However, ONRAB "Ultralite" (Artemis Technologies Inc., Guelph, Ontario, Canada) baits have been distributed by the United States Department of Agriculture (USDA) in select areas of the eastern United States under an experimental permit to target raccoons since 2011.{{cite journal | vauthors = Gilbert A, Johnson S, Walker N, Wickham C, Beath A, VerCauteren K | title = Efficacy of Ontario Rabies Vaccine Baits (ONRAB) against rabies infection in raccoons | journal = Vaccine | volume = 36 | issue = 32 Pt B | pages = 4919–4926 | date = August 2018 | pmid = 30037482 | doi = 10.1016/j.vaccine.2018.06.052 | s2cid = 51714285 | doi-access = free }} RABORAL V-RG 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. ONRAB "Ultralite" baits consist of a blister pack with a coating matrix of vanilla flavor, green food coloring, vegetable oil and hydrogenated vegetable fat. When an animal bites into the bait, the packets burst and the vaccine is administered.{{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)|access-date=18 November 2019|archive-date=14 November 2019|archive-url=https://web.archive.org/web/20191114054550/https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_rabies_vaccine_info|url-status=live}} Current research suggests that if adequate amounts of the vaccine is ingested, immunity to the virus should last for upwards of one year.{{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)|access-date=19 November 2019|archive-date=17 August 2020|archive-url=https://web.archive.org/web/20200817200000/https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_rabies_faqs|url-status=live}} 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. Landscape features such as large bodies of water and mountains are often used to enhance the effectiveness of the buffer.{{cite journal | vauthors = Algeo TP, Slate D, Caron RM, Atwood T, Recuenco S, Ducey MJ, Chipman RB, Palace M | display-authors = 6 | title = Modeling Raccoon (Procyon lotor) Habitat Connectivity to Identify Potential Corridors for Rabies Spread | journal = Tropical Medicine and Infectious Disease | volume = 2 | issue = 3 | pages = 44 | date = August 2017 | pmid = 30270901 | pmc = 6082097 | doi = 10.3390/tropicalmed2030044 | doi-access = free }} The effectiveness of ORV campaigns in specific areas is determined through trap-and-release methods.{{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}} Titer tests are performed on the blood drawn from the sample animals in order to measure rabies antibody levels in the blood. 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, they are distributed by hand in suburban or urban regions. The standard bait distribution density is 75 baits/km² in rural areas and 150 baits/km² in urban and developed areas.

Implementation of ORV programs in the United States has led to the elimination of the coyote rabies virus variant in 2003 and gray fox variant during 2013.{{cite journal | vauthors = Sidwa TJ, Wilson PJ, Moore GM, Oertli EH, Hicks BN, Rohde RE, Johnston DH | title = Evaluation of oral rabies vaccination programs for control of rabies epizootics in coyotes and gray foxes: 1995-2003 | journal = Journal of the American Veterinary Medical Association | volume = 227 | issue = 5 | pages = 785–792 | date = September 2005 | pmid = 16178403 | doi = 10.2460/javma.2005.227.785 | doi-access = free }}{{cite journal | vauthors = Blanton JD, Hanlon CA, Rupprecht CE | title = Rabies surveillance in the United States during 2006 | journal = Journal of the American Veterinary Medical Association | volume = 231 | issue = 4 | pages = 540–556 | date = August 2007 | pmid = 17696853 | doi = 10.2460/javma.231.4.540 | doi-access = free }} Furthermore, ORV has been successful in preventing the westward expansion of the raccoon rabies enzootic front beyond Alabama.

{{Reflist}}

• {{cite web | title=Imovax | website=U.S. Food and Drug Administration (FDA) | date=16 December 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/imovax | archive-url=https://web.archive.org/web/20200918100708/https://www.fda.gov/vaccines-blood-biologics/vaccines/imovax | url-status=dead | archive-date=18 September 2020 | id=STN: 103931 }}
• {{cite web | title=RabAvert - Rabies Vaccine | website=U.S. Food and Drug Administration (FDA) | date=19 December 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/rabavert-rabies-vaccine | archive-url=https://web.archive.org/web/20190930030127/https://www.fda.gov/vaccines-blood-biologics/vaccines/rabavert-rabies-vaccine | url-status=dead | archive-date=30 September 2019 | id=STN: BL 103334}}
• {{MeshName|Rabies Vaccines}}

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fr:Rage (maladie)#Histoire des vaccins