Blood serum containing antibodies; used to spread passive immunity
This article is about the applications of antiserum. For an explanation of its production, see polyclonal antibodies.
This article may require cleanup to meet Wikipedia's quality standards. The specific problem is: Dives too deep into monoclonal, which mostly isn’t produced by live humans (or domestic animals) donating their serum, even in "modern use"! Antiserum needs to be serum or derived from it. Please help improve this article if you can.(January 2023) ( Learn how and when to remove this template message )
Serum therapy, also known as serotherapy, describes the treatment of infectious disease using the serum of animals that have been immunized against the specific organisms or their product, to which the disease is supposedly referable.[citation needed]
Behring had pioneered the technique, using guinea pigs to produce serum.[2] Based on his observation that people who survived infection with the diphtheria bacterium never became infected again, he discovered that the body continually produces an antitoxin, which prevents survivors of infections from being infected again with the same agent.
It was necessary for Behring to immunize larger animals in order to produce enough serum to protect humans, because the amount of antiserum produced by guinea pigs was too little to be practical. Horses proved to be the best serum producer, as the serum of other large animals is not concentrated enough, and horses were not believed to carry any diseases that could be transferred to humans.
Due to the First World War, a large number of horses were needed for military purposes. It was difficult for Behring to find enough German horses for his serum facility. He chose to obtain horses from Eastern European countries, mostly Hungary and Poland. Because of Behring's limited financial resources, most horses he selected had been intended for slaughter; however, the usefulness of the animal to others had no influence on the production of serum. Serum horses were calm, well-mannered, and in good health. Age, breed, height, and color were irrelevant.[3]
Horses were transported from Poland or Hungary to the Behring facilities in Marburg, in the west-central part of Germany. Most of the horses were transported by rail and treated like any other freight load. During the interminable border crossing, horses were left at the mercy of the weather.[4] Once the horses arrived in Marburg, they had three to four weeks to recover in a quarantine facility, where data on them was recorded. They had to be in perfect medical condition for the immunization, and the quarantine facility ensured that they were free of microbes which could infect the other horses. In the Behring facilities, the horses were viewed as life savers; therefore, they were well treated. A few of the individual horses used for serum production were named, and celebrated for their service to medicine, both human and non-human.
At the end of the 19th century, every second child in Germany was infected with diphtheria, the most frequent cause of death in children up to 15 years. In 1891 Emil Behring saved the life of a young girl with diphtheria by injecting antiserum for the first time in history. Serum horses proved to be saviors of diphtheria-infected people. Subsequently, treatment of tetanus, rabies, and snake venom developed, and proactive protective vaccination against diphtheria and other microbial diseases began.
In 1984, Milstein and Köhler won a Nobel Prize for their paper that described their method for making murine monoclonal antibodies by immortalizing B cells as hybridomas. Another breakthrough occurred in 2003. A new technology allowed for heavy and light chain immunoglobulin genes to be amplified from human B cells and cloned into expression vectors. In 2008, this method was refined with a greater ability to sort cells and clone, which led to the discovery of more human monoclonal antibodies.
In 1996, the FDA approved the use of RSV-IGIV (Respigam), a polyclonal antibody drug to inhibit respiratory syncytial virus (RSV) for high-risk newborns. This was considered a breakthrough, as the clinical trial was proven to reduce infant hospitalizations by 41% and length of hospital stays by 53%. After two years the product demand began to exceed the supply of plasma and Synagis, the first humanized monoclonal antibody was approved in its place. Monoclonal antibodies became advantageous due to their decreased variability in quality, a decreased risk of bloodborne diseases, and increased potency. This enabled a large expansion of the usages of antiserum and opened the door for the treatment of autoimmune diseases.
The past 30 years have seen the transformation of how chronic and autoimmune diseases (e. g. cancer, ulcerative colitis) are treated, with 30 drugs—28 of which for chronic conditions—with monoclonal antibodies being approved. Monoclonal antibodies are currently being researched to treat viral diseases without vaccines, such as HIV, SARS, and MERS.[5]
Monoclonal antibodies are used to treat both acute and chronic conditions. Acute conditions may include, but are not limited to Ebola virus, envenomation (e. g. snake bites), and anthrax infection. Chronic conditions may include, but are not limited to rheumatoid arthritis, ulcerative colitis, and lupus.[6]
There are four main types of monoclonal antibodies. They are murine, chimeric, humanized, and human.
Murine monoclonal antibodies are identified with the suffix "-omab". They originate from a murine animal and can trigger allergic reactions in humans.[7] An example of a murine monoclonal antibody is Blinatumomab, which is used to treat acute lymphoblastic leukemia.[6]
Chimeric monoclonal antibodies are identified with the suffix "-ximab". They originate partially from a murine animal and partially from a human.[7] An example of a chimeric monoclonal antibody is Infliximab, which is used to treat Crohn disease.[6]
Humanized monoclonal antibodies are identified with the suffix "-zumab". They mostly originate from a human but differ in the component that attaches to its target.[7] An example of a humanized monoclonal antibody is Crizanlizumab, which treats sickle cell disease.[6]
Human monoclonal antibodies are identified with the suffix "-umab". They originate from a human.[7] An example of a human monoclonal antibody is Ustekinumab, which treats psoriasis.[6]
During the early stages of the COVID-19 pandemic, reliable treatment options had not yet been found or approved. In reaction, convalescent blood plasma was considered as a possibility and is used as a treatment option at least for severe cases.[8][9][10] In May 2021, India was one of the first major country to remove plasma from its national COVID-19 guideline. This was after public criticism on the lack of its effectiveness and health systems burdening from leading Indian scientists including Shahid Jameel, Soumyadeep Bhaumik, Gagandeep Kang, Soumitra Pathare, and others.[11][12][13][14] The World Health Organization recommended against use of plasma in COVID-19 in December 2021.[15]
Antibodies in the antiserum bind the infectious agent or antigen.[18] The immune system then recognizes foreign agents bound to antibodies and triggers a more robust immune response. The use of antiserum is particularly effective against pathogens which are capable of evading the immune system in their unstimulated state but are not robust enough to evade the stimulated immune system. The existence of antibodies to the agent depends on an initial survivor whose immune system, by chance, discovered a counteragent to the pathogen or a host species which carries the pathogen but does not experience its effects.[19] Further stocks of antiserum can then be produced from the initial donor or from a donor organism that is inoculated with the pathogen and cured by some stock of pre-existing antiserum. Diluted snake venom is often used as an antiserum to give passive immunity to snake venom itself.[20][21]
Horses that were infected by a pathogen were vaccinated thrice in increasing sizes of the dose. The time between each vaccination varied from each horse and its health condition. Normally the horses needed a few weeks to produce the serum in the blood after the last vaccination. Even though they tried to empower the immune system of the horses during this immunization with painstaking care, most of the horses experienced appetite loss, fever, and in worse cases shock and dyspnea.[citation needed]
The highest immunization risk for horses was the production of antiserum for snake venom.
The horse was immunized with all types of snake poison at the same time because it was not always possible to know by which snake species a person had been bitten. Therefore, the serum had to immunize the subject against the venom of every snake species.
In order to find the moment when most antitoxins in the blood cells of the horses is produced, frequent blood samples were taken from the horses. At the point when the highest amount of antibodies were produced, five liters of blood, a tenth of the blood volume of a horse, were taken through a cannula.
The blood was collected in a glass cylinder and brought to the laboratory in the Behring facilities. Above the rouleaux formation which contained the red blood cells, the serum was visible. The color of the serum varied from milky to brown.
Concentration and sterility of the serum were checked carefully, and the serum was filtered many times. Protein content was decreased in order to use the serum for humans.
After the blood sampling, the horses could rest for three to four weeks and received extra food to recover the blood loss. In this period the horses were especially weak and prone to disease and infection.
Within a few years, with experience and observation of the horses, a rouleaux formation of the blood sample was placed back into the animal's body. This procedure is called plasmapheresis.
Related Research Articles
Paul Ehrlich was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology, and antimicrobial chemotherapy. Among his foremost achievements were finding a cure for syphilis in 1909 and inventing the precursor technique to Gram staining bacteria. The methods he developed for staining tissue made it possible to distinguish between different types of blood cells, which led to the ability to diagnose numerous blood diseases.
Emil von Behring, born Emil Adolf Behring, was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded in that field, for his discovery of a diphtheria antitoxin. He was widely known as a "saviour of children", as diphtheria used to be a major cause of child death. His work with the disease, as well as tetanus, has come to bring him most of his fame and acknowledgment. He was honoured with Prussian nobility in 1901, henceforth being known by the surname "von Behring."
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.
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.
A monoclonal antibody is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a specific treatment for envenomation. It is composed of antibodies and used to treat certain venomous bites and stings. Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved. It is given by injection.
An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, they can also kill bacteria and other microorganisms. Antitoxins are made within organisms, and can be injected into other organisms, including humans, to treat an infectious disease. This procedure involves injecting an animal with a safe amount of a particular toxin. The animal's body then makes the antitoxin needed to neutralize the toxin. Later, blood is withdrawn from the animal. When the antitoxin is obtained from the blood, it is purified and injected into a human or other animal, inducing temporary passive immunity. To prevent serum sickness, it is often best to use an antitoxin obtained from the same species.
CSL Limited is an Australian multinational specialty biotechnology company that researches, develops, manufactures, and markets products to treat and prevent serious human medical conditions. CSL's product areas include blood plasma derivatives, vaccines, antivenom, and cell culture reagents used in various medical and genetic research and manufacturing applications. The company was established in 1916 as Commonwealth Serum Laboratories and was wholly owned by the Australian federal government until its privatisation in 1994.
Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body. They are a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.
Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.
Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes a target cell line, delivering lethal chemical doses. Antibodies are used to bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses. This is known as immune checkpoint therapy.
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.
CSL Behring is a biopharmaceutical company, manufacturing plasma-derived, and recombination therapeutic products. The company is a combination of Behringwerke, founded in 1904 in Marburg, Germany by Emil von Behring, and the Commonwealth Serum Laboratories (CSL), established in Australia in 1916 to provide vaccines to the people of Australia, as well as other companies acquired since 2004.
Diphtheria vaccine is a toxoid vaccine against diphtheria, an illness caused by Corynebacterium diphtheriae. Its use has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000. The first dose is recommended at six weeks of age with two additional doses four weeks apart, after which it is about 95% effective during childhood. Three further doses are recommended during childhood. It is unclear if further doses later in life are needed.
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.
COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.
Convalescent plasma is the blood plasma collected from a survivor of an infectious disease. This plasma contains antibodies specific to a pathogen and can be used therapeutically by providing passive immunity when transfusing it to a newly infected patient with the same condition. Convalescent plasma can be transfused as it has been collected or become the source material for the hyperimmune serum which consists largely of IgG but also includes IgA and IgM. or as source material for anti-pathogen monoclonal antibodies, Collection is typically achieved by apheresis, but in low-to-middle income countries, the treatment can be administered as convalescent whole blood.
Liise-anne Pirofski is a Professor of Medicine, Microbiology and Immunology at Albert Einstein College of Medicine and Montefiore Medical Center. She is a Member of the Association of American Physicians, and a Fellow of the American Association for the Advancement of Science, American Academy of Microbiology, American College of Physicians and the Infectious Diseases Society of America.
Passive antibody therapy, also called serum therapy, is a subtype of passive immunotherapy that administers antibodies to target and kill pathogens or cancer cells. It is designed to draw support from foreign antibodies that are donated from a person, extracted from animals, or made in the laboratory to elicit an immune response instead of relying on the innate immune system to fight disease. It has a long history from the 18th century for treating infectious diseases and is now a common cancer treatment. The mechanism of actions include: antagonistic and agonistic reaction, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC).
1 2 3 4 Miller, Justine (2016-08-08). "What is a Monoclonal Antibody?". National Institute for Cellular Biotechnology. National Institute for Cellular Biotechnology.
↑ de Andrade, Fábio Goulart; Eto, Silas Fernandes; Navarro dos Santos Ferraro, Ana Carolina; Gonzales Marioto, Denise Turini; Vieira, Narciso Júnior; Cheirubim, Ana Paula; de Paula Ramos, Solange; Venâncio, Emerson José (May 2013). "The production and characterization of anti-bothropic and anti-crotalic IgY antibodies in laying hens: A long term experiment". Toxicon. 66: 18–24. doi:10.1016/j.toxicon.2013.01.018. PMID23416799.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
