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The rabies vaccine is a
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
used to prevent
rabies Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
. There are a number of rabies vaccines available that are both safe and effective. 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. Doses are usually given by injection into the skin or muscle. After exposure, the vaccination is typically used along with rabies immunoglobulin. It is recommended that those who are at high risk of exposure be vaccinated before potential exposure. Rabies vaccines are effective in humans and other animals, and vaccinating dogs is very effective in preventing the spread of rabies to humans. A long-lasting immunity to the virus develops after a full course of treatment. Rabies vaccines may be used safely by all age groups. 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 Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
,
headaches Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resu ...
, or
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
. After exposure to rabies, there is no contraindication to its use, because the untreated virus is overwhelmingly fatal. The first rabies vaccine was introduced in 1885 and was followed by an improved version in 1908. Millions of people globally are vaccinated against the virus. It is on the World Health Organization's List of Essential Medicines.


Medical uses


Before exposure

The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(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.


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. 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. Because the rabies virus has a relatively long incubation period, post-exposure vaccinations are typically highly effective.


Additional doses

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.


Safety

Rabies vaccines are safe in all age groups. 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 Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
,
headaches Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resu ...
, or
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
. 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 World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
.


Types

The human
diploid Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectiv ...
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. 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. The vaccine was attenuated and prepared in the H.D.C. strain
WI-38 WI-38 is a diploid human cell line composed of fibroblasts derived from lung tissue of a 3-month-gestation female fetus. The fetus came from the elective abortion of a Swedish woman in 1963. She was disinterested in the fate of the fetus and its s ...
which was gifted to Dr. Hilary Koprowski at the Wistar Institute by Dr.
Leonard Hayflick Leonard Hayflick (born 20 May 1928) is a Professor of Anatomy at the UCSF School of Medicine, and was Professor of Medical Microbiology at Stanford University School of Medicine. He is a past president of the Gerontological Society of America and ...
, an Associate Member, who developed this normal human diploid cell strain. Verorab, developed by Sanofi-Aventis and Speeda, developed by Liaoning Chengda are purified vero cell rabies vaccine (PVRV). The first is approved by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
. Verorab is approved for medical use in Australia and the European Union and is
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosi ...
for both pre-exposure and post-exposure prophylaxis against rabies.


History

Virtually all infections with rabies resulted in death until two French scientists,
Louis Pasteur Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named afte ...
and
Émile Roux Pierre Paul Émile Roux FRS (17 December 18533 November 1933) was a French physician, bacteriologist and immunologist. Roux was one of the closest collaborators of Louis Pasteur (1822–1895), a co-founder of the Pasteur Institute, and respons ...
, 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. The treatment started with a
subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, c ...
on 6 July 1885, at 8:00pm, 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 In physics, attenuation (in some contexts, extinction) is the gradual loss of flux intensity through a medium. For instance, dark glasses attenuate sunlight, lead attenuates X-rays, and water and air attenuate both light and sound at var ...
, but later ones were progressively more virulent. 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. Neural tissue vaccines also carry a certain risk of neurological complications.


Society and culture


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 , while in Europe a course costs around . 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 The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(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.


Veterinary use

Pre-exposure
immunization Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-s ...
has been used on domesticated and wild populations. In many jurisdictions, domestic dogs, cats, ferrets, and rabbits are required to be vaccinated. 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. 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
ferret The ferret (''Mustela furo'') is a small, domesticated species belonging to the family Mustelidae. The ferret is most likely a domesticated form of the wild European polecat (''Mustela putorius''), evidenced by their interfertility. Other mus ...
s and, in some areas, pet skunks.


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 Dumaguete, officially the City of Dumaguete ( ceb, Dakbayan sa Dumaguete; fil, Lungsod ng Dumaguete), is a 3rd income class component city and the capital of the province of Negros Oriental, Philippines. According to the 2020 census, it has a p ...
in the
Philippines The Philippines (; fil, Pilipinas, links=no), officially the Republic of the Philippines ( fil, Republika ng Pilipinas, links=no), * bik, Republika kan Filipinas * ceb, Republika sa Pilipinas * cbk, República de Filipinas * hil, Republ ...
developed and produced a dog vaccine that gave a three-year immunity from
rabies Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
. The development of the vaccine resulted in the elimination of rabies in many parts of the
Visayas The Visayas ( ), or the Visayan Islands ( Visayan: ''Kabisay-an'', ; tl, Kabisayaan ), are one of the three principal geographical divisions of the Philippines, along with Luzon and Mindanao. Located in the central part of the archipelago, ...
and
Mindanao Mindanao ( ) ( Jawi: مينداناو) is the second-largest island in the Philippines, after Luzon, and seventh-most populous island in the world. Located in the southern region of the archipelago, the island is part of an island group of ...
Islands. The successful program in the Philippines was later used as a model by other countries, such as
Ecuador Ecuador ( ; ; Quechua: ''Ikwayur''; Shuar: ''Ecuador'' or ''Ekuatur''), officially the Republic of Ecuador ( es, República del Ecuador, which literally translates as "Republic of the Equator"; Quechua: ''Ikwadur Ripuwlika''; Shuar: ' ...
and the Yucatan State of Mexico, in their fight against rabies conducted in collaboration with the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
. In
Tunisia ) , image_map = Tunisia location (orthographic projection).svg , map_caption = Location of Tunisia in northern Africa , image_map2 = , capital = Tunis , largest_city = capital , ...
, 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 Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
based rabies vaccine only used countrywide. Vaccinations are often administered when owners take in their dogs for check-ups and visits at the vet. 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.


Wild animals

Wildlife species, primarily bats, raccoons, skunks, and foxes, act as reservoir species for different variants of the rabies virus. 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 vaccine

Oral rabies vaccines in pellet form are intended to be given to wild animals to produce a
herd immunity Herd immunity (also called herd effect, community immunity, population immunity, or mass immunity) is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become im ...
effect. The development of safe and effective rabies virus vaccines applied in attractive
bait Bait may refer to: General * Bait (luring substance), bait as a luring substance ** Fishing bait, bait used for fishing Film * ''Bait'' (1950 film), a British crime film by Frank Richardson * ''Bait'' (1954 film), an American noir film by Hugo ...
s resulted in the first field trials in Switzerland in 1978 to immunize red foxes. There are currently two different types of oral wildlife rabies vaccine in use: * Modified live virus: Attenuated vaccine strains of rabies virus such as SAG2 and SAD B19 * Recombinant vaccinia virus expressing rabies glycoprotein: This is a strain of the vaccinia virus (originally a smallpox vaccine) that has been engineed to encode the gene for the rabies glycoprotein. It is mostly used in the USA (raccoons, foxes, and coyotes) and in western Europe (red foxes) Other oral rabies experimental vaccines in development include recombinant
adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from ...
vaccines. 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 eradicate
rabies Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
in wild animal vectors of disease, mainly foxes,
raccoon The raccoon ( or , ''Procyon lotor''), sometimes called the common raccoon to distinguish it from other species, is a mammal native to North America. It is the largest of the procyonid family, having a body length of , and a body weight of ...
s,
raccoon dog The common raccoon dog (''Nyctereutes procyonoides''), also called the Chinese or Asian raccoon dog, is a small, heavy-set, fox-like canid native to East Asia. Named for its raccoon-like face markings, it is most closely related to foxes. Common ...
s,
coyote The coyote (''Canis latrans'') is a species of canine native to North America. It is smaller than its close relative, the wolf, and slightly smaller than the closely related eastern wolf and red wolf. It fills much of the same ecological nich ...
s and
jackal Jackals are medium-sized canids native to Africa and Eurasia. While the word "jackal" has historically been used for many canines of the subtribe canina, in modern use it most commonly refers to three species: the closely related black-backed ...
s, but also can be used for dogs in
developing countries A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
. 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. When an animal bites into the bait, the packets burst and the vaccine is administered. Current research suggests that if adequate amounts of the vaccine is ingested, immunity to the virus should last for upwards of one year. 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. The effectiveness of ORV campaigns in specific areas is determined through trap-and-release methods. 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, however, they are distributed by hand in suburban or urban regions. 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. The oral vaccine does not contain the whole rabies virus and has been proven safe in over 60 animal species including cats and dogs. The idea of
wildlife Wildlife refers to undomesticated animal species, but has come to include all organisms that grow or live wild in an area without being introduced by humans. Wildlife was also synonymous to game: those birds and mammals that were hunted ...
vaccination was conceived during the 1960s, and modified-live rabies viruses were used for the experimental oral vaccination of
carnivores A carnivore , or meat-eater (Latin, ''caro'', genitive ''carnis'', meaning meat or "flesh" and ''vorare'' meaning "to devour"), is an animal or plant whose food and energy requirements derive from animal tissues (mainly muscle, fat and other so ...
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.


References


External links

* * * * {{DEFAULTSORT:Rabies Vaccine Animal vaccines French inventions Inactivated vaccines Rabies Vaccines World Health Organization essential medicines (vaccines) Wikipedia medicine articles ready to translate fr:Rage (maladie)#Histoire des vaccins