Vaccine, Diphtheria

Adsorption. The adsorption of the components of a vaccine on to a mineral adjuvant. The mineral adjuvants, or carriers, most often used are aluminium lydroxide, aluminium phosphate and calcium phosphate and their effect is to increase the immunogenieity and decrease the toxicity, local and systemic, of a vaccine. Diphtheria vaccine, tetanus vaccine, diphtheria/tetanus vaccine and diphtheriaAetanus/pertussis vaccine are generally prepared as adsorbed vaccines. 

Diphtheria and tetanus vaccines are two commonly used toxoid-based vaccine preparations. The initial stages of diphtheria vaccine production entail the growth of Corynebacterium diphtheriae. 

Examples are diphtheria and tetanus vaccines. Diphtheria vaccine is produced by formaldehyde treatment of the toxin secreted by Corynebacterium diptheriae. Similarly, tetanus vaccine is obtained from toxins of cultured Clostridium tetani that has been treated with formaldehyde. 

Common childhood vaccines include the three-in-one measles, mumps and rubella and the diphtheria vaccine. Infectious mononucleosis, also knov/n as glandular fever, is caused by the Epstein-Barr virus and no vaccine is available. 

Diphtheria vaccine Diphtheria toxoid formed by treating diphtheria toxin with formaldehyde Active immunization against diphtheria... 

Diphtheria and tetanus vaeeine are two eommonly used toxoid-based vaccine preparations. The initial stages of diphtheria vaccine production entails the growth of Corynebacterium diphtheriae. The toxoid is then prepared by treating the active toxin produced with formaldehyde. The product is normally sold as a sterile aqueous preparation. Tetanus vaccine production follows a similar approach Clostridium tetani is cultured in appropriate media, the toxin is recovered and inactivated by formaldehyde treatment. Again, it is usually marketed as a sterile aqueous-based product. 

McNeela EA, Connor D, Gill J, et al. A mucosal vaccine against diphtheria. Vaccine 2000 19(9-10) 1188-1198. 

Johansen, P, Moon, L., Tamber, H., Merkle, H. P., Gander, B., and Sesardic, D. (1999), Immunogenicity of single-dose diphtheria vaccines based on PLA/PLGA microspheres in guinea pigs, Vaccine, 18, 209-215. 

Diphtheria vaccine contains diphtheria toxoid carried on aluminium hydroxide or calcium phosphate. Single antigen products are available only for cases in which combined antigens should not be used. The formulations used in most countries are a childhood formulation containing 25-30 Lf (flocculating units) of diphtheria toxoid (D) and an adult formulation containing 2 Lf of diphtheria toxoid (d). The formulations of choice in routine immunization are DTP (diphtheria and tetanus toxoids combined with pertussis vaccine), DT (diphtheria and tetanus toxoids) for pediatric use, and Td (tetanus and diphtheria toxoids with a limited amount of diphtheria antigen) for use in older children and adults. 

There have been comparisons of the immunogenicity and reactogenicity of different diphtheria vaccines. They have involved single or combined administration of diphtheria and/or tetanus toxoids (SEDA-13, 279) (SEDA-15, 345), booster immunization using Td vaccines including either aluminium hydroxide or calcium phosphate as adjuvant (SEDA-20, 288), or either plain or adsorbed formulations (SEDA-21, 328). 

In a study of adverse events after immunization in New Zealand in 1990-95 (3), reactions at the injection site after adult tetanus-diphtheria vaccine (68 reports per 100 000 immunizations) were reported five times more often than with tetanus vaccine. 

Ehrengut W. Komplikationen nach Diphtherieschutzimpfung und Impfungen mit Diphtherietoxoid-Mischimpfstoffen. [Neural compUcations after diphtheria vaccination and inocn-lations with diphtheria toxoid-mixed vaccines. Observations on their etiopathogenesis.] Dtsch Med Wochenschr 1986 lll(24) 939-42. 

Van der Wielen M, Van Damme P. Tetanus-diphtheria booster in non-responding tetanus-diphtheria vaccines. Vaccine 2000 19(9-10) 1005-6. 

There have been individual reports of fatal angio-immunoblastic lymphadenopathy, hemolytic uremic syndrome (after typhoid/paratyphoid/diphtheria vaccination), fatal hyperpyrexia (SED-11, 687), transverse myelitis (SEDA-10, 288), erythema nodosum (SEDA-11,289) (SEDA-14, 281), and Reiter s sjmdrome (SEDA-15, 350). 

The elderly suffer most in terms of increased morbidity and mortality when recommended vaccines are not administered. Pneumococcal diseases are the vaccine preventable diseases that cause, by far, the most mortality in the elderly.Unfortunately, the vaccine for pneumococcal-induced pneumonia has one of the lowest administration rates. Other vaccines that most elderly and longterm care residents should receive include the influenza and tetanus/diphtheria vaccines. Consultant pharmacists or pharmacists providing services to long-term care facilities are in excellent positions to identify those who need vaccines. 

The first group, mainly children with infections, shows persistent IgA and IgM deficiency. It is unusual to see any rise in IgG with infections, this being a useful pointer to its dubious quality. Responses to tetanus, pertussis, and diphtheria vaccines are poor, although some response usually occurs in TAB. Unlike the first case described, most others have shown isohemagglutinins. Lymphocytes have been normal in numbers and in transformation to PHA. The response to dinitrofluorobenzene was normal (D2), but other delayed hypersensitivity reactions have been variable, as has homograft rejection. The lymph nodes have varied from normal through primary follicles with no germinal centers (D2), to absence... 

Biological sources are primarily used for vaccines. Vaccines are suspensions of living or killed micro-organisms, components or products thereof. They are produced in living systems. Eggs are the most widely used medium at present, notably for influenza vaccines, but there is increasing use of animal cell cultures. Bacterial vaccines, for example, the diphtheria vaccine, can be cultured. There is an overlap here with fermentation processes (Section II.D.). 

In organ transplant recipients taking immunosuppressants, tetanus vaccines and inactivated polio vaccines produced protective antibody titres. The response to diphtheria vaccine was lower than in healthy controls and the antibody titre had fallen below the protective level by 12 months in 38% of patients in one study, and 24% in another. Note that live polio vaccines are not recommended in immunosuppressed patients (see Live vaccines, below). 

Gupta, R.K. Griffin, P.J. Rivera, R. Siber, G.R. Development of an animal model to assess the immu-nogenicity of single-dose tetanus and diphtheria vaccines based on controlled release from biodegradable polymer microspheres. Dev. Biol. Stand. 1998, 92, 277-287. 

Peyre M, Fleck R, Hockley D, Gander B, Sesardic D. In vivo uptake of an experimental microencapsulated diphtheria vaccine following sub-cutaneous immunisation. Vaccine. June 23, 2004 22(19) 2430-2437. PubMed PMID 15193406. 

In a study of neurodevelopment in infants at 6 months who had been exposed in utero to thimerosal in tetanus-diphtheria vaccines during pregnancy there were no differences from infants who had not been exposed [4Pf. Although there was a significant correlation between the concentration of mercury in the hair of the mothers and the hair of the neonates, there was no correlation between the degree of in utero exposure to ethylmercury and mercury concentrations in neonatal hair. 

Marques RC, D6rea JG, Bernardi JV. Thimerosal exposure (from tetanus-diphtheria vaccine) during pregnancy and neurodevelopment of breastfed infants at 6 months. Acta Paediatr 2010 99(6) 934—9. 

Rahman MM, Mahalanabis D, Hossain S, Wahed MA, Alvarez JO, Siber GR, Thompson C, Santosham M, Fuchs GJ. Simultaneous vitamin A administration at routine immunization contacts enhances antibody responses to diphtheria vaccine in infants younger than six months. J Nutr 1999 129(12) 2192-5. 

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%. 

Relyveld E.H. 1980. Current developments in production and testing of tetanus and diphtheria vaccines. In A. Mizrahi et al. (Eds.), Progress in Clinical and Biological Research, Vol. 47 New Developments with Human and Veterinary Vaccines, p. 51. New York, Alan R. Liss. 

---