Protein toxoids

Conjugates, which are vaccines that link a protein (toxoid) from an unrelated organism to the outer coat of the disease-causing microorganism. The result is a substance that is recognized by the immature immune system of young infants. Haemophilus influenzae type b is an example. 

C diphtheria vaccine is typical of a crude protein toxoid vaccine. Here the 58 kDa toxin is the antigen, and it is converted to a toxoid with formaldehyde and crudely purified. The cells are first separated from the toxin by centrifugation. Sometimes the pathogen culture is inactivated with formaldehyde before centrifugation. The supernate is treated with formaldehyde to 0.75%, and it is stored for 4 to 6 weeks at 37°C to allow complete detoxification (Pappenheimer, 1984]. The toxoid is then concentrated by ultrafiltration and fractionated from contaminants by ammonium sulfate precipitation. During detoxification of crude material, reactions with formaldehyde lead to a variety of products. The toxin is internally cross-linked and also cross-Hnked to other toxins, beef peptones from the medium, and other medium proteins. Because detoxification creates a population of molecules containing antigen, the purity of this product is only about 60 to 70%. 

Vaccines can be roughly categorized into killed vaccines and Hve vaccines. A killed vaccine can be (/) an inactivated, whole microorganism such as pertussis, (2) an inactivated toxin, called toxoid, such as diphtheria toxoid, or (J) one or more components of the microorganism commonly referred to as subunit vaccines. The examples are capsular polysaccharide of Streptococcus pneumoniae and the surface antigen protein for Hepatitis B vims vaccine. 

The U.S. standard pertussis vacciae is used to standardize the potency of the whole ceU pertussis vacciae. The number of protective units Hi the vaccine is estimated for each lot from the results of simultaneous intracerebral mouse-protection tests of the vaccine being studied and the U.S. reference standard (14,17). The potency of the aceUular vaccines is estimated by then abUity to produce antibodies to the proteins Hi the vaccine Hi a mouse model. These vaccines also undergo a series of animal safety tests to ensure that the iaactivation and toxoiding steps were carried out correctiy (14,17). 

The most common carrier proteins in use today are keyhole limpet hemocyanin (KLH MW 4.5 X 105 to 1.3 X 107), BSA (MW 67,000), aminoethylated (or cationized) BSA (cBSA), thyroglobulin (MW 660,000), ovalbumin (OVA MW 43,000), and various toxoid proteins, including tetanus toxoid and diphtheria toxoid. Other proteins occasionally used include myoglobin, rabbit serum albumin, immunoglobulin molecules (particularly IgG) from bovine or mouse sera, tuberculin purified protein derivative, and synthetic polypeptides such as poly-L-lysine and poly-L-glutamic acid. 

Since OVA and BSA possess some immunologically similar epitopes, a population of the antibodies produced against one often will cross-react against the other. Therefore, OVA cannot function as a non-relevant carrier for BSA and vice versa. Either OVA or BSA, however, may be used as non-relevant carriers for KLH, thyroglobulin, or the various toxoid proteins used as immunogen conjugates. 

Haemophilus b conjugate vaccine contains 25 micrograms of a purified capsular polysaccharide and 18 micrograms of diphtheria toxoid protein in a single dose of 0.5 mL. How many micrograms of diphtheria toxoid proteins are there in a vial containing 2.5 mL of the vaccine ... 

Schulze, K., Olive, C., Ebensen, T., and Guzman, C. A. (2006). Intranasal vaccination with Sfbl or M protein-derived peptides conjugated to diphtheria toxoid confers protective immunity against a lethal challenge with Streptococcus pyogenes. Vaccine 24, 6088-6095. 

Patients with protein-calorie malnutrition, especially children with marasmus and chest infections, had very high levels of serum IgD (R7). Antigen binding activity of IgD to diphtheria-toxoid and to bovine y-globulins in some human sera have been reported (G4, H3). 

In rabbits with undemutrition due to a shortage of calories there was a depressed agglutinin production against typhoid vaccine (C3, R4). A similar incapacity to produce antibodies to typhoid vaccine was reported in children with severe protein malnutrition (Bll). During treatment of 5 children, mean age 24 months, with chronic primary malnutrition, it was observed that their response to a single standard dose of 100 imits of purified diphtheroid toxoid was small and slow. Furthermore there was no correlation between specific antibody response and serum protein levels (02). 

Each lyophilisate for one immunising dose of diphtheria, tetanus toxoids and pertussis with Haemophilus b conjugate vaccine contains Haemophilus influenzae type b polysaccharide conjugated to tetanus protein 10 meg, purified diphtheria toxoid 1 immunising dose, purified tetanus toxoid 1 immunising dose, Bordetella pertussis minimum of 4.1 lU. 

There is a perceived need to develop effective vaccines against bovine spongiform encephalopathy (BSE) and the human form, new variant Creutzfeldt-Jacob (nvCJ) disease. Organ transplant vaccines would obviously be beneficial and tetanus toxoid has been shown to lower cholesterol in animals. Tumor-specific antigens have also been explored and heat stress proteins have been evaluated as adjuvants in this case. 

Other Bacterial vaccines and toxoids 1 Viral vaccines J Rickettsial vaccines Antisera Antiviral protein (interferon) Prophylaxis Therapy Chemotherapy Subunit vaccines sometimes available... 

The binding of proteins such as tetanus toxoid (TTd) onto dextran can also be achieved via thiolation. Therefore, dextran is converted selectively at the terminal reducing ends. This is possible either after amination and modification of the terminal amino function with 2-iminothiolan hydrochlo-... 

Cholera vaccines are produced by inactive bacteria and are administered subcutaneously, intramuscularly, or intradermally. Cholera vaccines should not be administered intradermally in children less than 5 years of age. The vaccination is particularly indicated for people living in highly endemic areas, as well as laboratory and medical personnel exposed to Vibrio cholerae. Diphtheria tetanus pertussis (DTP) vaccine can be made either as toxoids or inactivated whole bacteria. Hemophillus influenzae vaccine is a bacterial polysaccharide conjugated to proteins and is given as one intramuscular dose. A booster dose is not recommended. This vaccine is given to all children in cases such as plenia and other at-risk condiUons. 

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