An attenuated vaccine (or a live attenuated vaccine, LAV) is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live").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 virus (inactivated vaccine).
Attenuated vaccines stimulate a strong and effective immune response that is long-lasting.In comparison to inactivated vaccines, attenuated vaccines produce a stronger and more durable immune response with a quick immunity onset. Attenuated vaccines function by encouraging the body to create antibodies and memory immune cells in response to the specific pathogen which the vaccine protects against. Common examples of live attenuated vaccines are measles, mumps, rubella, yellow fever, and some influenza vaccines.
Viruses may be attenuated using the principles of evolution via serial passage of the virus through a foreign host species, such as:
The initial virus population is applied to a foreign host. Through natural genetic variability or induced mutation, a small percentage of the viral particles should have the capacity to infect the new host.These strains will continue to evolve within the new host and the virus will gradually lose its efficacy in the original host, due to lack of selection pressure. This process is known as "passage" in which the virus becomes so well adapted to the foreign host that it is no longer harmful to the subject that is to receive the vaccine. This makes it easier for the host immune system to eliminate the agent and create the immunological memory cells which will likely protect the patient if they are infected with a similar version of the virus in "the wild".
Viruses may also be attenuated via reverse genetics.Attenuation by genetics is also used in the production of oncolytic viruses.
Bacteria is typically attenuated by passage, similar to the method used in viruses.Gene knockout guided by reverse genetics is also used.
Attenuated vaccines can be administered in a variety of ways:
Vaccines function by encouraging the creation of cells, such as CD8+ and CD4+ T lymphocytes, or molecules, such as antibodies, that are specific to the pathogen.The cells and molecules can either prevent or reduce infection by killing infected cells or by producing interleukins. The specific effectors evoked can be different based on the vaccine. Live attenuated vaccines tend to help with the production of CD8+ cytotoxic T lymphocytes and T-dependent antibody responses. A vaccine is only effective for as long as the body maintains a population of these cells. Live attenuated vaccines can induce long-term, possibly lifelong, immunity without requiring multiple vaccine doses. Live attenuated vaccines can also induce cellular immune responses, which do not rely solely on antibodies but also involve immune cells such as cytotoxic T cells or macrophages.
Live-attenuated vaccines stimulate a strong and effective immune response that is long-lasting.Given pathogens are attenuated, it is extremely rare for pathogens to revert to their pathogenic form and subsequently cause disease. Additionally, within the five WHO-recommended live attenuated vaccines (tuberculosis, oral polio, measles, rotavirus, and yellow fever) severe adverse reactions are extremely rare. However, similar to any medication or procedure, no vaccine can be 100% safe or effective.
Individuals with compromised immune systems (e.g., HIV-infection, chemotherapy, combined immunodeficiencies) typically should not receive live-attenuated vaccines as they may not be able to produce an adequate and safe immune response.Household contacts of immunodeficient individuals are still able to receive most attenuated vaccines since there is no increased risk of infection transmission, with the exception being the oral polio vaccine.
As precaution, live-attenuated vaccines are not typically administered during pregnancy.This is due to the risk of transmission of virus between mother and fetus. In particular, the varicella and yellow fever vaccines have been shown to have adverse effects on fetuses and nursing babies.
Some live attenuated vaccines have additional common, mild adverse effects due to their administration route.For example, the live attenuated influenza vaccine is given nasally and is associated with nasal congestion.
Compared to inactivated vaccines, live-attenuated vaccines are more prone to immunization errors as they must be kept under strict conditions during the cold chain and carefully prepared (e.g., during reconstitution).
The history of vaccine development started with the creation of the smallpox vaccine by Edward Jenner in the late 18th century.Jenner discovered that inoculating a human with an animal pox virus would grant immunity against smallpox, a disease considered to be one of the most devastating in human history. Although the original smallpox vaccine is sometimes considered to be an attenuated vaccine due to its live nature, it was not strictly-speaking attenuated since it was not derived directly from smallpox. Instead, it was based on the related and milder cowpox disease. The discovery that diseases could be artificially attenuated came in the late 19th century when Louis Pasteur was able to derive an attenuated strain of chicken cholera. Pasteur applied this knowledge to develop an attenuated anthrax vaccine and demonstrating its effectiveness in a public experiment. The first rabies vaccine was subsequently produced by Pasteur and Emile Roux by growing the virus in rabbits and drying the affected nervous tissue.
The technique of cultivating a virus repeatedly in artificial media and isolating less virulent strains was pioneered in the early 20th century by Albert Calmette and Camille Guérin who developed an attenuated tuberculosis vaccine called the BCG vaccine.This technique was later used by several teams when developing the vaccine for yellow fever, first by Sellards and Laigret, and then by Theiler and Smith. The vaccine developed by Theiler and Smith proved to be hugely successful and helped establish recommended practices and regulations for many other vaccines. These include the growth of viruses in primary tissue culture (e.g., chick embryos), as opposed to animals, and the use of the seed stock system which uses the original attenuated viruses as opposed to derived viruses (done to reduce variance in vaccine development and decrease the chance of adverse effects). The middle of the 20th century saw the work of many prominent virologists including Sabin, Hilleman, and Enders, and the introduction of several successful attenuated vaccines, such as those against polio, measles, mumps, and rubella.
For many of the pathogens listed below there are many vaccines, the list below simply indicates that there are one (or more) attenuated vaccines for that particular pathogen, not that all vaccines for that pathogen are attenuated.
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease. 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 to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future. Vaccines can be prophylactic, or therapeutic. Some vaccines offer full sterilizing immunity, in which infection is prevented completely.
Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than 40 °C (104 °F), cough, runny nose, and inflamed eyes. Small white spots known as Koplik's spots may form inside the mouth two or three days after the start of symptoms. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms. Common complications include diarrhea, middle ear infection (7%), and pneumonia (6%). These occur in part due to measles-induced immunosuppression. Less commonly seizures, blindness, or inflammation of the brain may occur. Other names include morbilli, rubeola, red measles, and English measles. Both rubella, also known as German measles, and roseola are different diseases caused by unrelated viruses.
Mumps is a viral disease caused by the mumps virus. Initial symptoms are non-specific and include fever, headache, malaise, muscle pain, and loss of appetite. These symptoms are usually followed by painful swelling of the parotid glands, called parotitis, which is the most common symptom of infection. Symptoms typically occur 16 to 18 days after exposure to the virus and resolve within two weeks. About one third of infections are asymptomatic.
The MMR vaccine is a vaccine against measles, mumps, and rubella. 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 4 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.
Herd immunity is a form of indirect protection from infectious disease that can occur with some diseases when a sufficient percentage of a population has become immune to an infection, whether through previous infections or vaccination, thereby reducing the likelihood of infection for individuals who lack immunity. Immune individuals are unlikely to contribute to disease transmission, disrupting chains of infection, which stops or slows the spread of disease. The greater the proportion of immune individuals in a community, the smaller the probability that non-immune individuals will come into contact with an infectious individual.
Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild with half of people not realizing that they are infected. A rash may start around two weeks after exposure and last for three days. It usually starts on the face and spreads to the rest of the body. The rash is sometimes itchy and is not as bright as that of measles. Swollen lymph nodes are common and may last a few weeks. A fever, sore throat, and fatigue may also occur. Joint pain is common in adults. Complications may include bleeding problems, testicular swelling, encephalitis, and inflammation of nerves. Infection during early pregnancy may result in a miscarriage or a child born with congenital rubella syndrome (CRS). Symptoms of CRS manifest as problems with the eyes such as cataracts, deafness, as well as affecting the heart and brain. Problems are rare after the 20th week of pregnancy.
Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent.
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens irrespective of their antigenic make-up. Other components of the immune system adapt themselves to each new disease encountered and can generate pathogen-specific immunity.
Vaccine hesitancy is a delay in acceptance, or refusal of vaccines despite the availability of vaccine services. The term covers outright refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain about their use, or using certain vaccines but not others. "Anti-vaccinationism" refers to total opposition to vaccination; in more recent years, anti-vaccinationists have been known as "anti-vaxxers" or "anti-vax". Vaccine hesitancy is complex and context-specific, varying across time, place and vaccines. It can be influenced by factors such as lack of proper scientifically-based knowledge and understanding about how vaccines are made or how vaccines work, complacency, convenience, or even fear of needles.
Viral pneumonia is a pneumonia caused by a virus. Pneumonia is an infection that causes inflammation in one or both of the lungs. The pulmonary alveoli fill with fluid or pus making it difficult to breathe. Pneumonia can be caused by bacteria, viruses, fungi or parasites. Viruses are the most common cause of pneumonia in children, while in adults bacteria are a more common cause.
The MMRV vaccine combines the attenuated virus MMR vaccine with the addition of the chickenpox vaccine or varicella vaccine. The MMRV vaccine is typically given to children between one and two years of age.
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 the age of 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.
A breakthrough infection is a case of illness in which a vaccinated individual becomes sick from the same illness that the vaccine is meant to prevent. Simply, they occur when vaccines fail to provide immunity against the pathogen they are designed to target. Breakthrough infections have been identified in individuals immunized against a variety of different diseases including Mumps, Varicella, and Influenza. The character of breakthrough infections is dependent on the virus itself. Often, the infection in the vaccinated individual results in milder symptoms and is of a shorter duration than if the infection was contracted naturally.
A neurotropic virus is a virus that is capable of infecting nerve cells.
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 rates of vaccination within a population are greater than 92%, outbreaks of measles typically no longer occur; however, they may occur again if rates of vaccination decrease. 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.
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.
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.
Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein-Barr virus, rubella, varicella, mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C, as well as COVID-19, which has been seen to cause this in persons otherwise thought to have a "low risk" of the virus's effects.
Non-specific effects of vaccines are effects which go beyond the specific protective effects against the targeted diseases. Non-specific effects can be strongly beneficial by increasing protection against non-targeted infections. This has been shown with two live attenuated vaccines, BCG vaccine and measles vaccine, through multiple randomized controlled trials. Theoretically, non-specific effects of vaccines may be detrimental, increasing overall mortality despite providing protection against the target diseases. Although observational studies suggest that diphtheria-tetanus-pertussis vaccine (DTP) may be detrimental, these studies are at high risk of bias and have failed to replicate when conducted by independent groups.
Vaccine-induced viral shedding is a form of viral shedding following a viral infection caused by a statistically insignificant number of administrations of attenuated vaccines, which is a specific vaccine technology that uses an attenuated form of a live virus. The overwhelming majority of vaccines, however, are not attenuated vaccines, and therefore cannot cause vaccine-induced viral shedding, and only a statistically insignificant number of viral infections from those types of vaccines have ever been recorded.
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