Serum antitoxin

Following the administration of live oral cholera vaccine (containing the attenuated strain V. cholerae CVD 103-HgR, prepared from V. cholerae 01 strain 569B), there were significant rises in serum antitoxin concentrations and only few mild adverse effects (SED-13, 925). There was protective efficacy in 82-100% of healthy adult volunteers and no difference in adverse effects between 25 recipients of the vaccine and 26 controls (1). 

A randomized, double-blind, placebo-controUed trial using a live oral cholera vaccine (strain CVD 103, derived from the V. cholerae 01 classical Inaba strain 569B by deletion of the genes encoding the A subunit of cholera toxin) was conducted in 50 healthy Swiss adults. There was a significant rise in serum antitoxin titers in 76% of the volunteers. Two vaccinees reported watery stools after immunization (2). 

General reactions (seen in some older children and adults) are usually limited to brief fever sustained fever and other systemic reactions are uncommon unless the person has been hyperimmunized. After the administration of DT vaccine, local reactions, generally erythema and induration, with or without tenderness, can occur. In hyperimmunized cases, Arthus-type hypersensitivity reactions can occur. These characteristically severe local reactions generally start 2-8 hours after an injection. People who have such reactions usually have very high serum antitoxin concentrations and one should be careful not to administer a booster more than once every 10 years. 

In children aged 15-16 years receiving routine reinforcement tetanus immunization, adsorbed vaccine caused more intense and more frequent local reactions than did plain tetanus toxoid, and a higher incidence of pjrexia. The incidence of swelling and erythema at the inoculation site increased with serum antitoxin titre at the time of administration, whereas pain and tenderness were related to the presence of the aluminium hydroxide adjuvant (17). Based on similar experiences it has been widely recommended that plain and not adsorbed tetanus toxoid should be used when reinforcement of immunity to tetanus alone is desired. 

Antitoxin An antibody formed in response to and capable of neutralizing a biological poison, an animal serum containing antitoxins, or a solution of antibodies (e.g., diphtheria antitoxin and botulinum antitoxin) derived from the serum of animal immunized with specific antigens. Antitoxins are used to confer passive immunity and for treatment. 

Passage of the Vims Act, regulating therapeutic serums and antitoxins. Enforcement by the Hygienic Laboratory (later to become the National Institute of Health), Treasury Department. 

The regulation of biologically derived therapeutics actually has a long history, and has also continued to evolve (see Table 12.4) (Weissinger, 1989, Korwek, 1997). This history led to the PHS Act providing a somewhat mixed description of the products under its authority, which in turn serves to define biologies for CBER [A biologic is] any virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood... 

Treatment—Since C. botulinum toxin blocks the actions of nerves that activate muscles necessary for breathing, an antitoxin can be injected up to about 24 hours (based on monkey studies) after exposure to a lethal toxin dose and still prevent death. The two types of available antitoxins prepared from horse sera are trivalent (includes types A, B, E) and heptavalent (types A, B, C, D, E, F, and G) preparations. It should be noted that patients face a theoretical risk of developing serum sickness from such antitoxins. 

Tetanus antitoxin is routinely administered as part of the management of tetanus-prone wounds. The antibody preparation is purified from pooled serum/plasma of human donors who have been immunized with tetanus toxin. 

Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of all biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic serum, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. 

In 1798 Edward Tenner published the classc memoir, An Inquiry into the Causes and Effect of the Variolae Vacciniae, documenting how inoculation with cowpox protected humans against smallpox infection [1]. Louis Pasteur s formulation of the germ theory extended the understanding of this kind of protection against infection [1,2]. About 100 years later, isolation of the diphtheria bacihus and description of a protective substance (antitoxin) by Roux and Yersin demonstrated that the protective substance found in the serum of immunized animals can be transferred to susceptible animals and thereby confer passive immunity [4]. The antitoxin or... 

A irus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or deriva-... 

Botulism Botulism antitoxin, equine Consult the CDC.3 Treatment and prophylaxis of botulism. Available from the CDC.3 Ten to 20 percent incidence of serum reactions. 

Diphtheria Diphtheria antitoxin, equine 20,000-120,000 units IV or IM depending on the severity and duration of illness. Early treatment of respiratory diphtheria. Available from the CDC.3 Anaphylactic reactions in 7% of adults and serum reactions in 5-10% of adults. 

Injected forms of antibodies which have been generated in another body or animal can be isolated, purified, and administered as standard human immune serum globulin (ISG), and ISG plus preparation, or as an animal antiserum or antitoxin. Some serums which are available are those for rabies, snake and insect bites, botulism, and tetanus. Temporary immunity of up to six months to hepatitis can be imparted by one "gamma globulin" shot. More permanent active immunity is available to health care workers. 

The history of the development of antitoxins in combating bacterial infection dates back to the early beginnings of organized bacteriology. Belrring was tile first to show that animals that were immune to diphtheria contained, in their serum, factors which were capable of neutralizing the poisonous effect of the toxins derived from the diphtheria bacillus. While this work was earned out in 1890, prior to many of the great discoveries of mass immunization, and much later the antibiotics, there yet remains a place for antitoxins in medical treatment or prophylaxis for some diseases, such as tetanus and botulism,... 

Historically, antibodies have been obtained from the serum of animals. The serum contains a mixture of polyclonal antibodies. In 1890, Emil Behring immunized rabbits and mice against tetanus and diphtheria and reported that the antitoxin serum could protect against a lethal dose of the toxin. Since then, antisera have been used to protect from pathogens and toxins, but serum sickness was a major drawback for their clinical use. Antisera may produce immune responses, which could cause severe allergic reactions, and may even lead to anaphylactic shock and death. 

A therapeutic serum is a product obtained from blood by removing the clot or clot components and the blood cells. .. (4) An antitoxin is a product containing the soluble substances in serum or other body fluid of an immunized animal that specifically neutralizes the toxin against which it is immune. (5) A product is analogous...(ii) to a therapeutic serum if composed of whole blood or plasma or containing some organic constituent of product other than a hormone or an amino acid, derived from whole blood, plasma, or serum... 

An antitoxin is a product containing the soluble substance in serum or other body fluid of an immunized animal that specifically neutralizes the toxin against which the animal is immune. 

Newcomb RW, Ishizaka K, DeVald BL. Human IgG and IgA diphtheria antitoxins in serum, nasal fluids and saliva. I Immunol 1969 103(2) 215—24. 

Biologies as a class may be regulated as drugs but are defined within the Public Health Service Act [PHSA, 42 U.S.C. 262(a)] by category as a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of diseases or injuries of humans [12],... 

Some guidance may be obtained from the official definitions According to 21 CFR 600.3 a biological product means "... any virus, therapeutic serum, toxin, antitoxin or analogous product...". Further explanations state that a product is analogous... 

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