Artificial induction of immunity

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Artificial induction of immunity is immunization achieved by human efforts in preventive healthcare, as opposed to (and augmenting) natural immunity as produced by organisms' immune systems. It makes people immune to specific diseases by means other than waiting for them to catch the disease. The purpose is to reduce the risk of death and suffering, [1] that is, the disease burden, even when eradication of the disease is not possible. Vaccination is the chief type of such immunization, greatly reducing the burden of vaccine-preventable diseases.

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Immunity against infections that can cause serious illness is beneficial. Founded on a germ theory of infectious diseases, as demonstrated by Louis Pasteur's discoveries, modern medicine has provided means for inducing immunity against a widening range of diseases to prevent the associated risks from the wild infections. [1] It is hoped that further understanding of the molecular basis of immunity will translate to improved clinical practice in the future. [2]

Variolation and smallpox

The earliest recorded artificial induction of immunity in humans was by variolation or inoculation, which is the controlled infection of a subject with a less lethal natural form of smallpox (known as Variola Minor) to make him or her immune to re-infection with the more lethal natural form, Variola Major. This was practiced in ancient times in China and India, and imported into Europe, via Turkey, around 1720 by Lady Montagu and perhaps others. From England, the technique spread rapidly to the Colonies, and was also spread by African slaves arriving into Boston. [3] [4]

Variolation had the disadvantage that the inoculating agent used was still an active form of smallpox and, although less potent, could still kill the inoculee or spread in its full form to others nearby. However, as the risk of death from inoculation with Variola Minor was just 1% to 2%, as compared to the 20% risk of death from the natural form of smallpox, the risks of inoculation were generally considered acceptable. [3] [5] [6] [7] [8] [9]

Vaccination

In 1796, Edward Jenner FRS, a doctor and scientist who had practiced variolation, performed an experiment based on the folk-knowledge that infection with cowpox, a disease with minor symptoms which was never fatal, also conferred immunity to smallpox. [10] The idea was not new; it had been demonstrated some years earlier by Benjamin Jesty, who had not publicized his discovery. [11] In 1798, Jenner extended his observations by showing that cowpox could be passed from a lesion on one patient to others through four arm to arm transfers and that the last in the series was immune by exposing him to smallpox. Jenner described the procedure, distributed his vaccine freely, and provided information to help those hoping to establish their own vaccines. In 1798 he published his information in his famous Inquiry into the Causes and Effects...of the Cow Pox. He is credited with being the first to start detailed investigations of the subject and of bringing it to the attention of the medical profession. [12] Despite some opposition vaccination took over from variolation.

Jenner, like all members of the Royal Society in those days, was an empiricist. [13] [14] [15] The theory to support further advances in vaccination came later.

Germ theory

Main articles: Pasteur Louis Pasteur; Germ Theory: Germ theory of disease

In the second half of the 1800s Louis Pasteur perfected experiments which disproved the then-popular theory of spontaneous generation and from which he derived the modern theory of (infectious) disease. Using experiments based on this theory, which posited that specific microorganisms cause specific diseases, Pasteur isolated the infectious agent from anthrax. He then derived a vaccine by altering the infectious agent so as to make it harmless and then introducing this inactivated form of the infectious agents into farm animals, which then proved to be immune to the disease. [16]

Pasteur also isolated a crude preparation of the infectious agent for rabies. In a brave piece of rapid medicine development, he probably saved the life of a person who had been bitten by a clearly rabid dog by performing the same inactivating process upon his rabies preparation and then inoculating the patient with it. The patient, who was expected to die, lived, and thus was the first person successfully vaccinated against rabies. [17]

Anthrax is now known to be caused by a bacterium, and rabies is known to be caused by a virus. The microscopes of the time could reasonably be expected to show bacteria, but imaging of viruses had to wait until the development of electron microscopes with their greater resolving power in the 20th century.

Toxoids

Some diseases, such as tetanus, cause disease not by bacterial growth but by bacterial production of a toxin. Tetanus toxin is so lethal that humans cannot develop immunity to a natural infection, as the amount of toxin and time required to kill a person is much less than is required by the immune system to recognize the toxin and produce antibodies against it. [18] However the tetanus toxin is easily denatured losing its ability to produce disease, but leaving it able to induce immunity to tetanus when injected into subjects. The denatured toxin is called a toxoid. [19]

Adjuvants

The use of simple molecules such as toxoids for immunization tends to produce a low response by the immune system, and thus poor immune memory. However, adding certain substances to the mixture, for example adsorbing tetanus toxoid onto alum, greatly enhances the immune response (see Roitt etc. below). These substances are known as adjuvants. Several different adjuvants have been used in vaccine preparation. Adjuvants are also used in other ways in researching the immune system. [20]

A more contemporary approach for "boosting" the immune response to simpler immunogenic molecules (known as antigens) is to conjugate the antigens. Conjugation is the attachment to the antigen of another substance which also generates an immune response, thus amplifying the overall response and causing a more robust immune memory to the antigen. For example, a toxoid might be attached to a polysaccharide from the capsule of the bacteria responsible for most lobar pneumonia. [21] [22]

Temporarily induced immunity

Platypus: monotremes lack placental transfer of immunity Platypus.jpg
Platypus: monotremes lack placental transfer of immunity

Temporary immunity to a specific infection can be induced in a subject by providing the subject with externally produced immune molecules, known as antibodies or immunoglobulins. This was first performed (and is still sometimes performed) by taking blood from a subject who is already immune, isolating the fraction of the blood which contains antibodies (known as the serum), and injecting this serum into the person for whom immunity is desired. This is known as passive immunity, and the serum that is isolated from one subject and injected into another is sometimes called antiserum. Antiserum from other mammals, notably horses, has been used in humans with generally good and often life-saving results, but there is some risk of anaphylactic shock and even death from this procedure because the human body sometimes recognizes antibodies from other animals as foreign proteins. [19] Passive immunity is temporary, because the antibodies which are transferred have a lifespan of only about 3–6 months. [19] Every placental mammal (which includes humans) has experienced temporarily induced immunity by transfer of homologous antibodies from its mother across the placenta, giving it passive immunity to whatever its mother became immune to. [19] [23] [24] This allows some protection for the young while its own immune system is developing.

Synthetic (recombinant or cell-clone) human immunoglobulins can now be made, and for several reasons (including the risk of prion contamination of biological materials) are likely to be used more and more often. However, they are expensive to produce and are not in large-scale production as of 2013. [25] In the future it might be possible to artificially design antibodies to fit specific antigens, then produce them in large quantities to induce temporary immunity in people in advance of exposure to a specific pathogen, such as a bacterium, a virus, or a prion. At present, the science to understand this process is available but not the technology to perform it. [26]

See also

Related Research Articles

<span class="mw-page-title-main">Vaccination</span> Administration of a vaccine to protect against disease

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. However, some diseases, such as measles outbreaks in America, have seen rising cases due to relatively low vaccination rates in the 2010s – attributed, in part, to vaccine hesitancy. According to the World Health Organization, vaccination prevents 3.5–5 million deaths per year.

<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">Cowpox</span> Disease of humans and animals

Cowpox is an infectious disease caused by the cowpox virus (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more often from infected cats. The hands and face are most frequently affected and the spots are generally very painful.

<span class="mw-page-title-main">Smallpox vaccine</span> Vaccine against Variola virus

The smallpox vaccine is the first vaccine to have been developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox virus. Cowpox served as a natural vaccine until the modern smallpox vaccine emerged in the 20th century. From 1958 to 1977, the World Health Organization (WHO) conducted a global vaccination campaign that eradicated smallpox, making it the only human disease to be eradicated. Although routine smallpox vaccination is no longer performed on the general public, the vaccine is still being produced to guard against bioterrorism, biological warfare, and mpox.

<span class="mw-page-title-main">Immunization</span> Process by which an individuals immune system becomes fortified against an infectious agent

Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent.

In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization.

This is a timeline of the development of prophylactic human vaccines. Early vaccines may be listed by the first year of development or testing, but later entries usually show the year the vaccine finished trials and became available on the market. Although vaccines exist for the diseases listed below, only smallpox has been eliminated worldwide. The other vaccine-preventable illnesses continue to cause millions of deaths each year. Currently, polio and measles are the targets of active worldwide eradication campaigns.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

<span class="mw-page-title-main">DPT vaccine</span> Combination vaccine

The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis, and tetanus. The vaccine components include diphtheria and tetanus toxoids and either killed whole cells of the bacterium that causes pertussis or pertussis antigens. The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against to generate an immune response. In this way, the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease, rather than a vaccine which is targeted against the pathogen itself. The whole cells or antigens will be depicted as either "DTwP" or "DTaP", where the lower-case "w" indicates whole-cell inactivated pertussis and the lower-case "a" stands for "acellular". In comparison to alternative vaccine types, such as live attenuated vaccines, the DTP vaccine does not contain any live pathogen, but rather uses inactivated toxoid to generate an immune response; therefore, there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself. As a result, the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest.

<span class="mw-page-title-main">Conjugate vaccine</span> Type of vaccine

A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.

<span class="mw-page-title-main">Toxoid</span>

A toxoid is an inactivated toxin whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, whereas toxoids are altered form of toxins; toxoids are not secreted by bacteria. Thus, when used during vaccination, an immune response is mounted and immunological memory is formed against the molecular markers of the toxoid without resulting in toxin-induced illness. Such a preparation is also known as an anatoxin. There are toxoids for prevention of diphtheria, tetanus and botulism.

<span class="mw-page-title-main">Anthrax vaccine</span> Vaccines against the bacterium Bacillus anthracis

Anthrax vaccines are vaccines to prevent the livestock and human disease anthrax, caused by the bacterium Bacillus anthracis.

The following are notable events in the Timeline of immunology:

In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.

Immunization during pregnancy is the administration of a vaccine to a pregnant individual. This may be done either to protect the individual from disease or to induce an antibody response, such that the antibodies cross the placenta and provide passive immunity to the infant after birth. In many countries, including the US, Canada, UK, Australia and New Zealand, vaccination against influenza, COVID-19 and whooping cough is routinely offered during pregnancy.

<span class="mw-page-title-main">Hepatitis B vaccine</span> Vaccine against hepatitis B

Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended that health-care workers be vaccinated. In healthy people, routine immunization results in more than 95% of people being protected.

<span class="mw-page-title-main">Pertussis vaccine</span> Vaccine protecting against whooping cough

Pertussis vaccine is a vaccine that protects against whooping cough (pertussis). There are two main types: whole-cell vaccines and acellular vaccines. The whole-cell vaccine is about 78% effective while the acellular vaccine is 71–85% effective. The effectiveness of the vaccines appears to decrease by between 2 and 10% per year after vaccination with a more rapid decrease with the acellular vaccines. The vaccine is only available in combination with tetanus and diphtheria vaccines. Pertussis vaccine is estimated to have saved over 500,000 lives in 2002.

Variolation was the method of inoculation first used to immunize individuals against smallpox (Variola) with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result. Only 1–2% of those variolated died from the intentional infection compared to 30% who contracted smallpox naturally. Variolation is no longer used today. It was replaced by the smallpox vaccine, a safer alternative. This in turn led to the development of the many vaccines now available against other diseases.

Inoculation is the act of implanting a pathogen or other microbe or virus into a person or other organism. It is a method of artificially inducing immunity against various infectious diseases. The term "inoculation" is also used more generally to refer to intentionally depositing microbes into any growth medium, as into a Petri dish used to culture the microbe, or into food ingredients for making cultured foods such as yoghurt and fermented beverages such as beer and wine. This article is primarily about the use of inoculation for producing immunity against infection. Inoculation has been used to eradicate smallpox and to markedly reduce other infectious diseases such as polio. Although the terms "inoculation", "vaccination", and "immunization" are often used interchangeably, there are important differences. Inoculation is the act of implanting a pathogen or microbe into a person or other recipient; vaccination is the act of implanting or giving someone a vaccine specifically; and immunization is the development of disease resistance that results from the immune system's response to a vaccine or natural infection.

<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.

References

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  2. ↑ Palmer, Guy H.; McElwain, Terry F. (1995). "Molecular basis for vaccine development against anaplasmosis and babesiosis". Veterinary Parasitology. 57 (1–3): 233–53. doi:10.1016/0304-4017(94)03123-E. PMID   7597787.
  3. 1 2 "Variolation". Smallpox – A Great and Terrible Scourge. National Institutes of Health. Archived from the original on 2 May 2019. Retrieved 21 March 2018.
  4. ↑ White, Andrew Dickson (1898). "Theological Opposition to Inoculation, Vaccination and the use of Anaesthetics". A History of the Warfare of Science with Theology. New York: D. Appleton and Company. Archived from the original on 17 September 2008. Retrieved 13 March 2006.
  5. ↑ Boylston, A.; Williams, A. (2008). "Zabdiel Boylston's evaluation of inoculation against smallpox". Journal of the Royal Society of Medicine. 101 (9): 476–7. doi:10.1258/jrsm.2008.08k008. PMC   2587382 . PMID   18779251.
  6. ↑ Lettres Philosophiques. Voltaire.
  7. ↑ In fact, the mortality rate of the Varoiola Minor form of smallpox then found in Europe was 1–3% as opposed to 30–50% for the Variola Major type found elsewhere; however, blindness, infertility, and severe scarring were common. Figures from "The Search for Immunisation", In Our Time, BBC Radio 4 (2006).
  8. ↑ Letter of Lady Montagu reproduced at "Letter of Lady Mary Montagu". Archived from the original on 2 January 2004. Retrieved 18 April 2013. viewed 18 March 2006
  9. ↑ Wolfe, R. M; Sharp, LK (2002). "Anti-vaccinationists past and present". BMJ. 325 (7361): 430–32. doi:10.1136/bmj.325.7361.430. PMC   1123944 . PMID   12193361.
  10. ↑ Harris F "Edward Jenner and Vaccination" World Wide School Full text Archived 8 July 2001 at the Wayback Machine
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  12. ↑ Baxby, Derrick (1999). "Edward Jenner's Inquiry; a bicentenary analysis". Vaccine. 17 (4): 302–07. doi:10.1016/s0264-410x(98)00207-2. PMID   9987167.
  13. ↑ Guérin, N. (2007). "Histoire de la vaccination: De l'empirisme aux vaccins recombinants" [History of vaccination: from empiricism towards recombinant vaccines]. La Revue de Médecine Interne (in French). 28 (1): 3–8. doi:10.1016/j.revmed.2006.09.024. PMID   17092612.
  14. ↑ Vaccines – a Biography edited by Andrew W. Artenstein ISBN   978-1-4419-1107-0 [ page needed ]
  15. ↑ Gal, O.; Wolfe, C. "Empiricism and the Life Sciences in Early Modern Thought". The University of Sydney. Archived from the original on 2 January 2023. Retrieved 18 April 2013.
  16. ↑ Smith, Alice Lorraine (1985). Principles of Microbiology. Times Mirror/Mosby College Pub. ISBN   978-0-8016-4685-0. Archived from the original on 14 January 2023. Retrieved 10 October 2016.
  17. ↑ René Dubos, Louis Pasteur: Freelance of Science, Little, Brown and Company, 1950.[ ISBN missing ][ page needed ]
  18. ↑ "Pathogenic Clostridia, including Botulism and Tetanus (page 3)". Todar's Online Textbook of Bacteriology. Archived from the original on 15 May 2021. Retrieved 21 March 2010.
  19. 1 2 3 4 Roitt, I.M. (1977). Essential Immunology 3rd Edition. Blackwell Scientific Publications. ISBN   063200276X.[ page needed ]
  20. ↑ "Overview". Archived from the original on 13 July 2013. Retrieved 18 April 2013.[ full citation needed ]
  21. ↑ http://www.merck.com/product/usa/pi_circulars/p/pneumovax_23/pneumovax_pi.pdf Archived 2 January 2023 at the Wayback Machine [ bare URL PDF ]
  22. ↑ Nuorti, J.P.; Whitney, C.G. (10 December 2010). Prevention of Pneumococcal Disease Among Infants and Children – Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine (Report). Centers for Disease Control and Prevention (CDC).
  23. ↑ Ehrlich, P. (1892) Ueber Immunitaet durch Vererbung und Saeugung. Z. Hyg. Infect. Kr. 12, 183.
  24. ↑ Pitcher-Wilmott, RW; Hindocha, P; Wood, CB (1980). "The placental transfer of IgG subclasses in human pregnancy". Clinical and Experimental Immunology. 41 (2): 303–08. PMC   1537014 . PMID   7438556.
  25. ↑ "Engineers of small-scale humanised antibody production. Prices on application". Archived from the original on 10 March 2016. Retrieved 16 April 2013.
  26. ↑ Immunisation article in Ganfyd, the online collaborative textbook of medicine. http://www.ganfyd.org/index.php?title=Artificial_induction_of_immunity
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