Vaccination

Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating the body's adaptive immunity, they help prevent sickness from an infectious disease. When a sufficiently large percentage of a population has been vaccinated, herd immunity results. Herd immunity protects those who may be immunocompromised and cannot get a vaccine because even a weakened version would harm them.

The effectiveness of vaccination has been widely studied and verified. Vaccination is the most effective method of preventing infectious diseases; widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox and the elimination of diseases such as polio and tetanus from much of the world. According to the World Health Organization (WHO), vaccination prevents 3.5–5 million deaths per year. A WHO-funded study by The Lancet estimates that, during the 50-year period starting in 1974, vaccination prevented 154 million deaths, including 146 million among children under age 5. However, some diseases have seen rising cases due to relatively low vaccination rates attributable partly to vaccine hesitancy.

The first disease people tried to prevent by inoculation was most likely smallpox, with the first recorded use of variolation occurring in the 16th century in China. It was also the first disease for which a vaccine was produced. Although at least six people had used the same principles years earlier, the smallpox vaccine was invented in 1796 by English physician Edward Jenner. He was the first to publish evidence that it was effective and to provide advice on its production. Louis Pasteur furthered the concept through his work in microbiology. The immunization was called vaccination because it was derived from a virus affecting cows ( 'cow'). When smallpox was finally eradicated in 1979, it had already killed an estimated 300–500 million people in the 20th century.

Vaccination and immunization have a similar meaning in everyday language. This is distinct from inoculation, which uses unweakened live pathogens. Vaccination efforts have been met with some reluctance on scientific, ethical, political, medical safety, and religious grounds, although no major religions oppose vaccination, and some consider it an obligation due to the potential to save lives. In the United States, people may receive compensation for alleged injuries under the National Vaccine Injury Compensation Program. Early success brought widespread acceptance, and mass vaccination campaigns have greatly reduced the incidence of many diseases in numerous geographic regions. The US Centers for Disease Control and Prevention lists vaccination as one of the ten great public health achievements of the 20th century in the US.

Mechanism of function

thumb|upright=1|In Sweden, [[polio vaccination started in 1957.]]

thumb|A mobile medicine laboratory providing vaccinations against diseases spread by [[ticks]]

thumb|COVID-19 Vaccination Center of the [[Medical University of Gdańsk, Poland]]

Vaccines are a way of artificially activating the immune system to protect against infectious disease. The activation occurs through priming the immune system with an immunogen. Stimulating immune responses with an infectious agent is known as immunization. Vaccination includes various ways of administering immunogens.

Most vaccines are administered before a patient has contracted a disease to help increase future protection. However, some vaccines are administered after the patient already has contracted a disease. Vaccines given after exposure to smallpox are reported to offer some protection from disease or may reduce the severity of disease. The first rabies immunization was given by Louis Pasteur to a child after he was bitten by a rabid dog. Since its discovery, the rabies vaccine has been proven effective in preventing rabies in humans when administered several times over 14 days along with rabies immune globulin and wound care. Other examples include experimental AIDS, cancer and Alzheimer's disease vaccines. Such immunizations aim to trigger an immune response more rapidly and with less harm than natural infection.

Most vaccines are given by injection as they are not absorbed reliably through the intestines. Live attenuated polio, rotavirus, some typhoid, and some cholera vaccines are given orally to produce immunity in the bowel. While vaccination provides a lasting effect, it usually takes several weeks to develop. This differs from passive immunity (the transfer of antibodies, such as in breastfeeding), which has immediate effect.

A vaccine failure is when an organism contracts a disease in spite of being vaccinated against it. Primary vaccine failure occurs when an organism's immune system does not produce antibodies when first vaccinated. Vaccines can fail when several series are given and fail to produce an immune response. The term "vaccine failure" does not necessarily imply that the vaccine is defective. Most vaccine failures are simply due to individual variations in immune response.

alt=|thumb|Measles infection rate vs. vaccination rate, 1980–2011. Source: [[World Health Organization|WHO]]

Vaccination versus inoculation

The term "inoculation" is often used interchangeably with "vaccination." However, while related, the terms are not synonymous. Vaccination is treatment of an individual with an attenuated (i.e. less virulent) pathogen or other immunogen, whereas inoculation, also called variolation in the context of smallpox prophylaxis, is treatment with unattenuated variola virus taken from a pustule or scab of a smallpox patient into the superficial layers of the skin, commonly the upper arm. Variolation was often done 'arm-to-arm' or, less effectively, 'scab-to-arm', and often caused the patient to become infected with smallpox, which in some cases resulted in severe disease.

Vaccinations began in the late 18th century with the work of Edward Jenner and the smallpox vaccine.

Preventing disease versus preventing infection

Some vaccines, like the smallpox vaccine, prevent infection. Their use results in sterilizing immunity and can help eradicate a disease if there is no animal reserve. Other vaccines, including those for , help to (temporarily) lower the chance of severe disease for individuals, without necessarily reducing the probability of becoming infected.

Safety

thumb|Global [[smallpox cases from 1920 to 2010. Source: WHO]]

Vaccine development and approval

Just like any medication or procedure, no vaccine can be 100% safe or effective for everyone because each person's body can react differently. While minor side effects, such as soreness or low grade fever, are relatively common, serious side effects are very rare and occur in about 1 out of every 100,000 vaccinations and typically involve allergic reactions that can cause hives or difficulty breathing.

However, vaccines are the safest they ever have been in history and each vaccine undergoes rigorous clinical trials to ensure their safety and efficacy before approval by authorities such as the US Food and Drug Administration (FDA).

Prior to human testing, vaccines are tested on cell cultures and the results modelled to assess how they will interact with the immune system.

After regulatory approval, the regulators continue to monitor the manufacturing protocols, batch purity, and the manufacturing facility itself. Additionally, vaccines also undergo phase IV trials, which monitor the safety and efficacy of vaccines in tens of thousands of people, or more, across many years.

Pandemrix a vaccine for the H1N1 pandemic of 2009 given to around 31 million people In a response to the narcolepsy reports following immunization with Pandemrix, the CDC carried out a population-based study and found the FDA-approved 2009 H1N1 flu shots were not associated with an increased risk for the neurological disorder.

Ingredients

The ingredients of vaccines can vary greatly from one to the next and no two vaccines are the same. The CDC has compiled a list of vaccines and their ingredients that is readily accessible on their website.

Aluminium

Aluminium is an adjuvant ingredient in some vaccines. An adjuvant is a type of ingredient that is used to help the body's immune system create a stronger immune response after receiving the vaccination. Aluminium is in a salt form (the ionic version of an element) and is used in the following compounds: aluminium hydroxide, aluminium phosphate, and aluminium potassium sulfate. For a given element, the ion form has different properties from the elemental form. Although it is possible to have aluminium toxicity, aluminium salts have been used effectively and safely since the 1930s when they were first used with the diphtheria and tetanus vaccines.

Mercury

Certain vaccines once contained a compound called thiomersal or thimerosal, which is an organic compound containing mercury. Organomercury is commonly found in two forms. The methylmercury cation (with one carbon atom) is found in mercury-contaminated fish and is the form that people might ingest in mercury-polluted areas (Minamata disease), whereas the ethylmercury cation (with two carbon atoms) is present in thimerosal, linked to thiosalicylate. Although both are organomercury compounds, they do not have the same chemical properties and interact with the human body differently. Ethylmercury is cleared from the body faster than methylmercury and is less likely to cause toxic effects. Even though evidence supports the safety and efficacy of thimerosal in vaccines, thimerosal was removed from childhood vaccines in the United States in 2001 as a precaution.

Vaccine Adverse Event Reporting System (VAERS)

|Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER)

|Immunization Action Coalition (IAC)

Vaccine Safety Datalink (VSD)

|Health Resources and Service Administration (HRSA)

|Institute for Safe Medication Practices (ISMP)

Clinical Immunization Safety Assessment (CISA) Project

National Institutes of Health (NIH)

National Vaccine Program Office (NVPO)

The administration protocols, efficacy, and adverse events of vaccines are monitored by organizations of the US federal government, including the Centers for Disease Control and Prevention and the Food and Drug Administration. As with all medications, vaccine use is determined by public health research, surveillance, and reporting to governments and the public.

One study estimated the energy required for produce 15.6 billion vaccines as ~10.8 billion kWh, resulting in the emissions of ~5.13 million tons in CO2eq.

Usage

thumb|upright=1.6|Share of children who received key vaccines in 2016

thumb|upright=1.6|Global vaccination coverage among one year olds (1980–2019)

Vaccination has saved 154 million lives, 95% of whom are children younger than five years of age.

The World Health Organization (WHO) has estimated that vaccination prevents 3.5–5 million deaths per year, They estimate that 29% of deaths of children under five-years-old in 2013 were vaccine preventable. In other developing parts of the world, they are faced with the challenge of having a decreased availability of resources and vaccinations. Countries such as those in Sub-Saharan Africa cannot afford to provide the full range of childhood vaccinations.

In 2024, a WHO/UNICEF report found "the number of children who received three doses of the vaccine against diphtheria, tetanus and pertussis (DTP) in 2023 – a key marker for global immunization coverage – stalled at 84% (108 million). However, the number of children who did not receive a single dose of the vaccine increased from 13.9 million in 2022 to 14.5 million in 2023. More than half of unvaccinated children live in the 31 countries with fragile, conflict-affected and vulnerable settings."

United States

Vaccines have led to major decreases in the prevalence of infectious diseases in the United States. In 2007, studies regarding the effectiveness of vaccines on mortality or morbidity rates of those exposed to various diseases found almost 100% decreases in death rates, and about a 90% decrease in exposure rates. Vaccination adoption is reduced among some populations, such as those with low incomes, people with limited access to health care, and members of certain racial and ethnic minorities. Distrust of health-care providers, language barriers, and misleading or false information also contribute to lower adoption, as does anti-vaccine activism.

Most government and private health insurance plans cover recommended vaccines at no charge when received by providers in their networks. The federal Vaccines for Children Program and the Social Security Act are among the major sources of financial support for vaccination of those in lower-income groups.

The Centers for Disease Control and Prevention (CDC) publishes uniform national vaccine recommendations and immunization schedules, although state and local governments, as well as nongovernmental organizations, may have their own policies.

History

thumb|upright=0.8|An 1802 testimonial to the efficacy of vaccination, presented to its pioneer, [[Edward Jenner, and signed by 112 members of the Physical Society, London]]

The earliest hints of the practice of variolation for smallpox in China date back to the 10th century. The oldest documented use of variolation comes from Wan Quan's Douzhen Xinfa (痘疹心法), published in 1549. They implemented a method of "nasal insufflation" administered by blowing powdered smallpox material, usually scabs, up the nostrils. Various insufflation techniques have been recorded throughout the sixteenth and seventeenth centuries within China. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers. In France, Voltaire reports that the Chinese have practiced variolation "these hundred years".

In 1796, Edward Jenner, a doctor in Berkeley in Gloucestershire, England, tested a common theory that a person who had contracted cowpox would be immune from smallpox. To test the theory, he took cowpox vesicles from a milkmaid named Sarah Nelmes, with which he infected an eight-year-old boy named James Phipps. Two months later he inoculated the boy with smallpox, and smallpox did not develop. In 1798, Jenner published An Inquiry Into the Causes and Effects of the Variolæ Vaccinæ which created widespread interest. He distinguished 'true' and 'spurious' cowpox (which did not give the desired effect) and developed an "arm-to-arm" method of propagating the vaccine from the vaccinated individual's pustule. Early attempts at confirmation were confounded by contamination with smallpox, but despite controversy within the medical profession and religious opposition to the use of animal material, by 1801 his report was translated into six languages and over 100,000 people were vaccinated. The term vaccination was coined in 1800 by the surgeon Richard Dunning in his text Some observations on vaccination.

thumb|upright=1.6|Queens of [[Kingdom of Mysore|Mysore: left, king Krishnaraja Wadiyar III's first wife, Devajammani, right, the king's second wife, also named Devajammani, center: Lakshmi Ammani, the king's grandmother. Thomas Hickey, 1805. The two queens in the painting are thought to advertise vaccination over variolation, as they display the respective traces on their skin: discoloration around the nose and mouth (left, variolation), or a small hidden scar (right, vaccination).]]

In 1802, the Scottish physician Helenus Scott vaccinated dozens of children in Bombay against smallpox using Jenner's cowpox vaccine. In the same year Scott penned a letter to the editor in the Bombay Courier, declaring that "We have it now in our power to communicate the benefits of this important discovery to every part of India, perhaps to China and the whole eastern world". Subsequently, vaccination became firmly established in British India. A vaccination campaign was started in the new British colony of Ceylon in 1803. By 1807 the British had vaccinated more than a million Indians and Sri Lankans against smallpox. Following a smallpox epidemic in 1816 the Kingdom of Nepal ordered smallpox vaccine and requested the English veterinarian William Moorcroft to help in launching a vaccination campaign. Following a smallpox epidemic in 1837 that caused 40,000 deaths, the British government initiated a concentrated vaccination policy, starting with the Vaccination Act 1840, which provided for universal vaccination and prohibited variolation. The law followed a severe outbreak of smallpox in 1851 and 1852. It provided that the poor law authorities would continue to dispense vaccination to all free of charge, but that records were to be kept on vaccinated children by the network of births registrars.]]

The U.S. Supreme Court upheld compulsory vaccination laws in the 1905 landmark case Jacobson v. Massachusetts, ruling that laws could require vaccination to protect the public from dangerous communicable diseases. However, in practice the U.S. had the lowest rate of vaccination among industrialized nations in the early 20th century. Compulsory vaccination laws began to be enforced in the U.S. after World War II. In 1959, the WHO called for the eradication of smallpox worldwide, as smallpox was still endemic in 33 countries. In the 1960s six to eight children died each year in the U.S. from vaccination-related complications. According to the WHO there were in 1966 about 100 million cases of smallpox worldwide, causing an estimated two million deaths. In the 1970s there was such a small risk of contracting smallpox that the U.S. Public Health Service recommended for routine smallpox vaccination to be ended. By 1974 the WHO smallpox vaccination program had confined smallpox to parts of Pakistan, India, Bangladesh, Ethiopia and Somalia. In 1977 the WHO recorded the last case of smallpox infection acquired outside a laboratory in Somalia. In 1980 the WHO officially declared the world free of smallpox.

UNICEF has reported on the extent to which children missed out on vaccinations from 2020 onwards due to the COVID-19 pandemic. By summer 2023, the organisation described vaccination programs as getting "back on track".

Vaccination policy

thumb|upright=1.2|Vaccination rate by US state, including exemptions allowed by state in 2017

To eliminate the risk of outbreaks of some diseases, at various times governments and other institutions have employed policies requiring vaccination for all people. For example, an 1853 law required universal vaccination against smallpox in England and Wales, with fines levied on people who did not comply. Common contemporary U.S. vaccination policies require that children receive recommended vaccinations before entering public school.

Beginning with early vaccination in the nineteenth century, these policies were resisted by a variety of groups, collectively called antivaccinationists, who object on scientific, ethical, political, medical safety, religious, and other grounds. Common objections are that vaccinations do not work, that compulsory vaccination constitutes excessive government intervention in personal matters, or that the proposed vaccinations are not sufficiently safe. Many modern vaccination policies allow exemptions for people who have compromised immune systems, allergies to the components used in vaccinations or strongly held objections.

In countries with limited financial resources, limited vaccination coverage results in greater morbidity and mortality due to infectious disease. More affluent countries are able to subsidize vaccinations for at-risk groups, resulting in more comprehensive and effective coverage. In Australia, for example, the Government subsidizes vaccinations for seniors and indigenous Australians.

Public Health Law Research, an independent US based organization, reported in 2009 that there is insufficient evidence to assess the effectiveness of requiring vaccinations as a condition for specified jobs as a means of reducing incidence of specific diseases among particularly vulnerable populations; that there is sufficient evidence supporting the effectiveness of requiring vaccinations as a condition for attending child care facilities and schools; and that there is strong evidence supporting the effectiveness of standing orders, which allow healthcare workers without prescription authority to administer vaccine as a public health intervention.

Fractional dose vaccination

Fractional dose vaccination reduces the dose of a vaccine to allow more individuals to be vaccinated with a given vaccine stock, trading societal benefit for individual protection. Based on the nonlinearity properties of many vaccines, it is effective in poverty diseases and promises benefits in pandemic waves, e.g. in COVID-19, when vaccine supply is limited.

Litigation

Allegations of vaccine injuries in recent decades have appeared in litigation in the U.S. Some families have won substantial awards from sympathetic juries, even though most public health officials have said that the claims of injuries were unfounded. In response, several vaccine makers stopped production, which the US government believed could be a threat to public health, so laws were passed to shield manufacturers from liabilities stemming from vaccine injury claims. Some concerns from families might have arisen from social beliefs and norms that cause them to mistrust or refuse vaccinations, contributing to this discrepancy in side effects that were unfounded.

Opposition

thumb|upright=1.75|Global survey across 67 countries responding to the question: "Overall I think vaccines are safe". This image depicts the distribution of responses that replied "Strongly disagree" or "Tend to disagree" with the previous statement.

Opposition to vaccination, from a wide array of vaccine critics, has existed since the earliest vaccination campaigns. Some studies have claimed to show that current vaccine schedules increase infant mortality and hospitalization rates.

Various disputes have arisen over the morality, ethics, effectiveness, and safety of vaccination. Some vaccination critics say that vaccines are ineffective against disease or that vaccine safety studies are inadequate. and some political groups oppose mandatory vaccination on the grounds of individual liberty. Some parents believe vaccinations cause autism, although there is no scientific evidence to support this idea. In 2011, Andrew Wakefield, a leading proponent of the theory that MMR vaccine causes autism, was found to have been financially motivated to falsify research data and was subsequently stripped of his medical license. In the United States people who refuse vaccines for non-medical reasons have made up a large percentage of the cases of measles, and subsequent cases of permanent hearing loss and death caused by the disease.

Many parents do not vaccinate their children because they feel that diseases are no longer present due to vaccination. This is a false assumption, since diseases held in check by immunization programs can and do still return if immunization is dropped. These pathogens could possibly infect vaccinated people, due to the pathogen's ability to mutate when it is able to live in unvaccinated hosts.

Vaccination and autism

The notion of a connection between vaccines and autism originated in a 1998 paper whose lead author was the physician Andrew Wakefield. His study concluded that eight of the twelve patients, aged three years of age to 10 years of age, developed behavioral symptoms consistent with autism following the administration of the MMR vaccine (an immunization against measles, mumps, and rubella). The article was widely criticized for lack of scientific rigor and it was proven that Wakefield falsified data in the article. In 2010, The Lancet officially retracted the article, stating that several elements of the article were incorrect, including falsified data and protocols. The article has sparked a much greater anti-vaccination movement, particularly in the United States, and even though the article was shown to be fraudulent and was heavily retracted, one in four parents still believe that vaccines can cause autism.

All validated and definitive studies have shown that there is no correlation between vaccines and autism. One of the studies published in 2015 confirms there is no link between autism and the MMR vaccine. Infants were given a health plan, that included an MMR vaccine, and were continuously studied until they reached five years old. There was no link between the vaccine and children who had a normally developed sibling or a sibling that had autism making them a higher risk for developing autism themselves.

It can be difficult to correct the memory of humans when wrong information is received prior to correct information. Even though there is much evidence to go against the Wakefield study and retractions were published by most of the co-authors, many people continue to believe and base decisions on the study as it still lingers in their memory. Studies and research are being conducted to determine effective ways to correct misinformation in the public memory.

Routes of administration

A vaccine administration may be oral, by injection (intramuscular, intradermal, subcutaneous), by puncture, transdermal or intranasal. Several recent clinical trials have aimed to deliver the vaccines via mucosal surfaces to be up-taken by the common mucosal immunity system, thus avoiding the need for injections.

Economics of vaccination

Health is often used as one of the metrics for determining the economic prosperity of a country. This is because healthier individuals are generally better suited to contributing to the economic development of a country than the sick. There are many reasons for this. For instance, a person who is vaccinated for influenza not only protects themselves from the risk of influenza, but simultaneously also prevents themselves from infecting those around them. This leads to a healthier society, which allows individuals to be more economically productive. Children are consequently able to attend school more often and have been shown to do better academically. Similarly, adults are able to work more often, more efficiently, and more effectively.

Costs and benefits

On the whole, vaccinations induce a net benefit to society. Vaccines are often noted for their high Return on investment (ROI) values, especially when considering the long-term effects. Some vaccines have much higher ROI values than others. Studies have shown that the ratios of vaccination benefits to costs can differ substantially—from 27:1 for diphtheria/pertussis, to 13.5:1 for measles, 4.76:1 for varicella, and 0.68–1.1: 1 for pneumococcal conjugate. The paper "represents the largest assessment of vaccine impact before COVID-19-related disruptions".

They estimated that it would cost between $2.8 billion and $3.7 billion to develop at least one vaccine for each of them. This should be set against the potential cost of an outbreak. The 2003 SARS outbreak in East Asia cost $54 billion.

Game theory uses utility functions to model costs and benefits, which may include financial and non-financial costs and benefits. In recent years, it has been argued that game theory can effectively be used to model vaccine uptake in societies. Researchers have used game theory for this purpose to analyse vaccination uptake in the context of diseases such as influenza and measles.

Gallery

File:Vaccination; "Dr Jenner performing his first vaccination, 17 Wellcome V0018142.jpg|Dr Jenner performing his first vaccination on James Phipps, a boy of age 8. 14 May 1796. Painting by Ernest Board (early 20th century)

File:The cow pock.jpg|James Gillray's The Cow-Pock—or—the Wonderful Effects of the New Inoculation!, an 1802 caricature of vaccinated patients who feared it would make them sprout cowlike appendages

File:Londre wellcome institute boilly vaccinee.jpg|La vaccine or Le préjugé vaincu by Louis-Léopold Boilly, 1807

File:A doctor vaccinating a small girl, other girls with loosened Wellcome V0016682.jpg|A doctor vaccinating a small girl, other girls with loosened blouses wait their turn apprehensively by Lance Calkin

File:'Serum straight from the horse'., inoculation caricature Wellcome L0009827.jpg|German caricature showing von Behring extracting the serum with a tap

File:The history of vaccination seen from an economic point of vi Wellcome V0011691.jpg|Les Malheurs de la Vaccine (The history of vaccination seen from an economic point of view: A pharmacy up for sale; an outmoded inoculist selling his premises; Jenner, to the left, pursues a skeleton with a lancet)

</gallery>

References

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External links

Vaccine Safety U.S. Centers for Disease Control and Prevention (CDC)
Vaccine History Timeline Immunize.org
Immunizations, vaccines and biologicals World Health Organization