Antitoxin inactivation

Toxoids are inactivated bacterial toxins. They retain the ability to stimulate the formation of antitoxin, which are antibodies directed against the bacterial toxin. Adjuvants are inert substances, such as aluminum salts (i.e., alum), which enhance vaccine antigenicity by prolonging antigen absorption. 

Another example that can be included in the subunit vaccine class is the use of bacterial toxoids. Many bacteria produce toxins which play an important role in the development of the disease caused by a particular organism. Thus, vaccines against some agents, for example tetanus and diphtheria, consist of the toxin inactivated with formaldehyde conjugated to an adjuvant. Immunization protects from disease by stimulating antitoxin antibody which neutralizes the effects of the toxin. 

A vaccine consists of a suspension of live (attenuated) or killed (inactivated) microorganisms (in whole or fractions), whereas a toxoid is a detoxified bacterial toxin that has the ability to trigger the production of antitoxin once administered into the body. 

Upon entry into the eytoplasm, fragment A catalyzes the ADP ribosylation of the transfer faetor, EF-2, leading to its inaetivation and the interruption of protein synthesis. The ADP-ribose group is donated by NAD+. The ADP ribosylation reaction, catalyzed by the toxin, is specific for EF-2 of eukaryotic cells other proteins of eukaryotic and bacterial eells are not substrates. This speeificity is due to an unusual amino acid residue in EF-2, diphthamide, which is the acceptor of the ADP ribosyl group. Diphthamide derives from the posttranslational modification of histidine. The acute symptoms are treated with antitoxin. The bacteria, which are gram-positive, succumb to a variety of antibiotics, including penicillin. Diphtheria is effectively prevented by immunization with toxoid (inactivated toxin) preparations. 

D. Heavy Metals Mercury and silver precipitate proteins and inactivate sulfhydryl groups of enzymes but are used rarely because of toxicity. Organic mercurials such as nitromersol and thimerosal frequently cause hypersensitivity reactions but continue to be used as preservatives for vaccines, antitoxins, and immune sera. Merbromin is a weak antiseptic and stains tissues a bright red color. In the past silver nitrate was commonly used for prevention of neonatal gonococcal ophthalmia, but it has been largely replaced by topical antibiotics. Silver sulfadiazine (a sulfonamide) is used to decrease bacterial colonization in bums. 

Although the total B-cell population has been low due to the lymphopenia the 7oPBM s recognised as B cells remains normal, as have serum and secretory immunoglobulins. Immunoelectrophoresis has shown no monoclonal band. Sero-conversion to respiratory syncytial virus has been noted (litre 1/10,1/40,1/10 at 6,12, and 16 months respectively. The patient was immunised with diptheria and tetanus toxoid plus inactivated polio vaccine at 4,6 and 12 months. No polio antibodies were detected but following tetanus immunisation 1-2 units/ml tetanus antitoxin were produced. There has been no response to intradermal Candida antigen at 6,12, and 15 months of age. 

Hewitt (255) showed that diphtheria toxin was inactivated by formaldehyde but not by sodium hydrosulfite or HjOj. The oxidizing or reducing powers of formaldehyde were therefore presumably not responsible for its action. It was also claimed (236) that toxoids formed at pH 6.3 bound more antitoxin than those prepared at pH 8.6. 

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