Rabies vaccine

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Rabies vaccine
Rabies vaccine.png
Vaccine description
Target Rabies
Vaccine type Inactivated
Clinical data
Trade names RabAvert, Rabipur, Rabivax, others
AHFS/Drugs.com Monograph
MedlinePlus a607023
License data
Pregnancy
category
Routes of
administration 		Intramuscular, intradermal
ATC code
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The rabies vaccine is a vaccine used to prevent rabies. [11] There are several rabies vaccines available that are both safe and effective. [11] Vaccinations must be administered prior to rabies virus exposure or within the latent period after exposure to prevent the disease. [12] Transmission of rabies virus to humans typically occurs through a bite or scratch from an infectious animal, but exposure can occur through indirect contact with the saliva from an infectious individual. [12]

Contents

Doses are usually given by injection into the skin or muscle. [11] After exposure, the vaccination is typically used along with rabies immunoglobulin. [11] It is recommended that those who are at high risk of exposure be vaccinated before potential exposure. [11] Rabies vaccines are effective in humans and other animals, and vaccinating dogs is very effective in preventing the spread of rabies to humans. [11] A long-lasting immunity to the virus develops after a full course of treatment. [11]

Rabies vaccines may be used safely by all age groups. [11] 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. [11] After exposure to rabies, there is no contraindication to its use, because the untreated virus is virtually 100% fatal. [11] [13]

The first rabies vaccine was introduced in 1885 and was followed by an improved version in 1908. [14] Millions of people globally are vaccinated against the virus. [11] It is on the World Health Organization's List of Essential Medicines. [15] [16]

Medical uses

Before exposure

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. [11] Other groups may include veterinarians, researchers, or people planning to travel to regions where rabies is common. [17] Three doses of the vaccine are given over a one-month period on days zero, seven, and either twenty-one or twenty-eight. [11] [17]

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. [18] This is known as post-exposure vaccination. [19] For people who have previously been vaccinated, only a single dose of the rabies vaccine is required. [19] 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. [19] Because the rabies virus has a relatively long incubation period, post-exposure vaccinations are typically highly effective. [11]

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. [11] Those at risk may have tests done to measure the amount of rabies antibodies in the blood, and then get rabies boosters as needed. [17] Following administration of a booster dose, one study found 97% of immunocompetent individuals demonstrated protective levels of neutralizing antibodies after ten years. [20]

Safety

Rabies vaccines are safe in all age groups. [11] [21] 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. [11] Because of the certain fatality of the virus, receiving the vaccine is always advisable. [11]

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. [11] Their use is thus not recommended by the World Health Organization. [11]

Types

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. [22]

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. [11] 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. [11] [23]

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. [24] [25]

Verorab, developed by Sanofi-Aventis and Speeda, developed by Liaoning Chengda are purified vero cell rabies vaccine (PVRV). [26] [27] The first is approved by the World Health Organization. [28] 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. [4] [10]

History

Early-20th-century rabies vaccination in Santa Catarina, Brazil Aplicacao de vacina anti-rabica.jpg
Early-20th-century rabies vaccination in Santa Catarina, 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. [29] The treatment started with a subcutaneous injection on 6 July 1885, at 8:00 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. [30]

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. [31] Neural tissue vaccines also carry a certain risk of neurological complications. [32]

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 US$1,000, while in Europe a course costs around €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. [33]

Veterinary use

Baits with vaccine for oral vaccination Lysvulpen.jpg
Baits with vaccine for oral vaccination
Machine for distribution of baits from airplane Oral vaccination.jpg
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. [34]

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

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. [36]

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 [37] 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. [38]

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. [39]

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. [40]

Wild animals

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. [41] [42] This results in the general occurrence of rabies as well as outbreaks in animal populations. [41] Approximately 90% of all reported rabies cases in the US are from wildlife. [41]

Oral rabies vaccine

Oral rabies vaccines are distributed across the landscape, targeting reservoir species, in an effort to produce a herd immunity effect. [43] 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. [44] Development of an oral immunization for wildlife began in the United States with laboratory trials using the live, attenuated Evelyn-Rokitnicki-Abselseth (ERA) vaccine, derived from the Street Alabama Dufferin (SAD) strain. [45] The first ORV field trial using the live attenuated vaccine to immunize foxes occurred in Switzerland during 1978. [46] [47]

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 [48]
  • 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. [49] [45] 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 [50] [51]

Other oral rabies experimental vaccines in development include recombinant adenovirus vaccines. [52]

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. [41] ORV programs were initiated in Europe in the 1980s, Canada in 1985, and in the United States in 1990. [53] 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. [54] 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. [45] 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. [55] 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. [41] ONRAB "Ultralite" baits consist of a blister pack with a coating matrix of vanilla flavor, green food coloring, vegetable oil and hydrogenated vegetable fat. [51] When an animal bites into the bait, the packets burst and the vaccine is administered. [53] Current research suggests that if adequate amounts of the vaccine is ingested, immunity to the virus should last for upwards of one year. [56] 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. [53] Landscape features such as large bodies of water and mountains are often used to enhance the effectiveness of the buffer. [57] The effectiveness of ORV campaigns in specific areas is determined through trap-and-release methods. [58] Titer tests are performed on the blood drawn from the sample animals in order to measure rabies antibody levels in the blood. [58] 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. [53] The standard bait distribution density is 75 baits/km2 in rural areas and 150 baits/km2 in urban and developed areas. [45]

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. [59] [60] Furthermore, ORV has been successful in preventing the westward expansion of the raccoon rabies enzootic front beyond Alabama. [43]

Related Research Articles

<span class="mw-page-title-main">Vaccine</span> Pathogen-derived preparation that provides acquired immunity to an infectious disease

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. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and recognize further and destroy any of the microorganisms associated with that agent that it may encounter in the future.

<span class="mw-page-title-main">MMR vaccine</span> Any of several combined vaccines against measles, mumps, and rubella

The MMR vaccine is a vaccine against measles, mumps, and rubella, abbreviated as MMR. The first dose is generally given to children around 9 months to 15 months of age, with a second dose at 15 months to 6 years of age, with at least four weeks between the doses. After two doses, 97% of people are protected against measles, 88% against mumps, and at least 97% against rubella. The vaccine is also recommended for those who do not have evidence of immunity, those with well-controlled HIV/AIDS, and within 72 hours of exposure to measles among those who are incompletely immunized. It is given by injection.

<span class="mw-page-title-main">Polio vaccine</span> Vaccine to prevent poliomyelitis

Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.

<span class="mw-page-title-main">Influenza vaccine</span> Vaccine against influenza

Influenza vaccines, colloquially known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945.

Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine against smallpox and mpox, having fewer side effects than smallpox vaccines derived from other poxviruses.

<span class="mw-page-title-main">Mumps vaccine</span> Vaccine which prevents mumps

Mumps vaccines are vaccines which prevent mumps. When given to a majority of the population they decrease complications at the population level. Effectiveness when 90% of a population is vaccinated is estimated at 85%. Two doses are required for long term prevention. The initial dose is recommended between 12 and 18 months of age. The second dose is then typically given between two years and six years of age. Usage after exposure in those not already immune may be useful.

<span class="mw-page-title-main">Varicella vaccine</span> Vaccine to prevent chickenpox

Varicella vaccine, also known as chickenpox vaccine, is a vaccine that protects against chickenpox. One dose of vaccine prevents 95% of moderate disease and 100% of severe disease. Two doses of vaccine are more effective than one. If given to those who are not immune within five days of exposure to chickenpox it prevents most cases of disease. Vaccinating a large portion of the population also protects those who are not vaccinated. It is given by injection just under the skin. Another vaccine, known as zoster vaccine, is used to prevent diseases caused by the same virus – the varicella zoster virus.

<span class="mw-page-title-main">Polio eradication</span> Effort to permanently eliminate all cases of poliomyelitis infection

Polio eradication, the permanent global cessation of circulation of the poliovirus and hence elimination of the poliomyelitis (polio) it causes, is the aim of a multinational public health effort begun in 1988, led by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF) and the Rotary Foundation. These organizations, along with the U.S. Centers for Disease Control and Prevention (CDC) and The Gates Foundation, have spearheaded the campaign through the Global Polio Eradication Initiative (GPEI). Successful eradication of infectious diseases has been achieved twice before, with smallpox in humans and rinderpest in ruminants.

An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable. Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the pathogen.

<span class="mw-page-title-main">Hepatitis A vaccine</span> Vaccine to prevent hepatitis A

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<span class="mw-page-title-main">Rabies</span> Deadly viral disease, transmitted through animals

Rabies is a viral disease that causes encephalitis in humans and other mammals. It was historically referred to as hydrophobia due to the symptom of panic when presented with liquids to drink. Early symptoms can include fever and abnormal sensations at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, the result is virtually always death, regardless of treatment. The time period between contracting the disease and the start of symptoms is usually one to three months but can vary from less than one week to more than one year. The time depends on the distance the virus must travel along peripheral nerves to reach the central nervous system.

Almost all human deaths caused by rabies occur in Asia and Africa.

<span class="mw-page-title-main">Rabies in animals</span> Deadly zoonotic disease

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<span class="mw-page-title-main">Measles vaccine</span> Vaccine used to prevent measles

Measles vaccine protects against becoming infected with measles. Nearly all of those who do not develop immunity after a single dose develop it after a second dose. When the rate of vaccination within a population is greater than 92%, outbreaks of measles typically no longer occur; however, they may occur again if the rate of vaccination decreases. The vaccine's effectiveness lasts many years. It is unclear if it becomes less effective over time. The vaccine may also protect against measles if given within a couple of days after exposure to measles.

<span class="mw-page-title-main">Rubella vaccine</span> Vaccine used to prevent rubella

Rubella vaccine is a vaccine used to prevent rubella. Effectiveness begins about two weeks after a single dose and around 95% of people become immune. Countries with high rates of immunization no longer see cases of rubella or congenital rubella syndrome. When there is a low level of childhood immunization in a population it is possible for rates of congenital rubella to increase as more women make it to child-bearing age without either vaccination or exposure to the disease. Therefore, it is important for more than 80% of people to be vaccinated. By introducing rubella containing vaccines, rubella has been eradicated in 81 nations, as of mid-2020.

<span class="mw-page-title-main">Inactivated vaccine</span> Vaccine using a killed version of a disease pathogen

An inactivated vaccine is a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed to destroy disease-producing capacity. In contrast, live vaccines use pathogens that are still alive. Pathogens for inactivated vaccines are grown under controlled conditions and are killed as a means to reduce infectivity and thus prevent infection from the vaccine.

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<span class="mw-page-title-main">Rabies in Haiti</span> Viral disease in Haiti

Rabies is a viral disease that exists in Haiti and throughout the world. It often causes fatal inflammation of the brain in humans and other mammals, such as dogs and mongooses in Haiti. The term "rabies" is derived from a Latin word that means "to rage"; rabid animals sometimes appear to be angry. Early symptoms can include fever and tingling at the site of exposure, followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, death is nearly always the outcome. The time period between contracting the disease and showing symptoms is usually one to three months; however, this time period can vary from less than a week to more than a year. The time between contraction and the onset of symptoms is dependent on the distance the virus must travel to reach the central nervous system.

<span class="mw-page-title-main">Animal vaccination</span> Process

Animal vaccination is the immunisation of a domestic, livestock or wild animal. The practice is connected to veterinary medicine. The first animal vaccine invented was for chicken cholera in 1879 by Louis Pasteur. The production of such vaccines encounter issues in relation to the economic difficulties of individuals, the government and companies. Regulation of animal vaccinations is less compared to the regulations of human vaccinations. Vaccines are categorised into conventional and next generation vaccines. Animal vaccines have been found to be the most cost effective and sustainable methods of controlling infectious veterinary diseases. In 2017, the veterinary vaccine industry was valued at US$7 billion and it is predicted to reach US$9 billion in 2024.

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