Aluminium hydroxide adjuvant

The rHBsAg is produced in an engineered S. cerevisiae strain and is likely purified subsequent to fermentation by a procedure somewhat similar to that presented in Figure 13.10. The final product is presented as a sterile suspension of the antigen absorbed onto aluminium hydroxide (adjuvant), in either single-use vials or pre-filled syringes. It also contains NaCl and phosphate buffer components as excipients. It is intended for i.m. injection, usually as 10 pg in a volume of 0.5 ml for infants/children or 20 pg (in 1.0 ml) for adults. The normal dosage schedule entails initial administration followed by boosters after 1 and 6 months. 

Hepatitis B vaccine (inactivated B virus surface antigen adsorbed on aluminium hydroxide adjuvant) provides active immunity against hepatitis B infection, and in coimtries of low endemicity it is given to individuals at high risk, including healthcare professionals. Immunity is conferred for at least 5 years and can be supplemented by booster injections. 

Aluminium hydroxide (adjuvant/adsorbant) Aluminium allergy, skin nodules [7,70]... 

Brewer, J.M. Conacher, M. Hunter, C.A. Mohrs, M. Brombacher, F. Alexander, J. Aluminium hydroxide adjuvant initiates strong antigen-specific Th2 responses in the absence of IL-4- or IL-13-mediated signaling. J. Immunol. 1999, 163, 6448-6454. 

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. 

Alhydrogeh, aluminium hydroxide adjuvant aluminium oxy-hydroxide poorly crystalline boehmite pseudoboehmite Rehydragel. 

Recently, an aluminium hydroxide-adjuvanted E. tarda vaccine was prepared and injected i.p in Japanese flounder. The resultant protection was found give an RPS of 69% (Jiao et al. 2010a). Immunisation with the antigen alone gave an RPS of 34%, so in this system alum seemed to be a promising adjuvant. However, when FIA was used an RPS of 81% was seen, thus showing that the oil adjuvant would be a more promising line of research. 

Presence of aluminium and calcium. The quantity of aluminium in vaccines containing aluminium hydroxide or aluminium phosphate as an adjuvant is limited to 1.25 mg per dose and it is nsnally estimated compleximetrically. The qnantity of calcium is limited to 1.3 mg per dose and is usually estimated by flame photometry. 

A number of mineral-based substances display an adjuvant effect. Although calcium phosphate, calcium chloride and salts of various metals (e.g. zinc sulfate and cerium nitrate) display some effect, aluminium-based substances are by far the most potent. Most commonly employed are aluminium hydroxide and aluminium phosphate (Table 13.13). Their adjuvanticity, coupled to their proven safety, render them particularly valuable in the preparation of vaccines for young children. They have been incorporated into millions of doses of such vaccine products so far. 

The principal method by which aluminium adjuvanted vaccines are prepared entails mixing the antigen in solution with a preformed aluminium phosphate (or hydroxide) precipitate under chemically defined conditions (e.g. of pH). Adsorption of the antigen to the aluminium-based gel ensues, with such preparations being generally termed aluminium-adsorbed vaccines 1 mg of aluminium hydroxide will usually adsorb in the order of 50-200 pg of protein. 

Mineral Salts Immunostimulatory adjuvants Lipid particles Particulate adjuvants Mucosal adjuvants Aluminium hydroxide, aluminium phosphate, calcium phosphate Saponins (e.g., QS21), MDP derivatives, bacterial DNA (CpG oligos), LPS, MPL and synthetic derivatives, lipopeptides, cytokines (e.g., GM-CSF, IL-2, IL-12) Liposomes, virosomes, iscoms, cochleates, emulsions (e.g., Freunds adjuvant, SAF, MF59 ) Poloxamer particles, virus-like particles, PLG microparticles Cholera toxin (CT), mutant toxin (e.g., LTK63, LTR72), heat labile enterotoxin (LT), microparticles, polymerized liposomes, chitosan... 

For this reason vaccine formulation tends to follow the traditional routes innovative formulations are rare. Aluminium hydroxide, aluminium phosphate and calcium phosphate are still the only registered vaccine adjuvants for humans. Veterinary vaccines have to rely on the same components, however, a few vaccines containing a mineral oil adjuvant (Marcol) or saponin (Quil A or derivatives) have passed the registration hurdles. It remains to be seen whether and under which restrictions these adjuvants can be used in the EEC after 1996 (see also below in "Additional requirements for veterinary products"). 

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). 

To increase immunogenicity, the hepatitis A vaccines commercially available are coupled to adjuvant aluminium phosphate or aluminium hydroxide. However, alum precipitates provoke inflammatory responses at the injection site. Immunostimulating reconstituted influenza virosomes have therefore been used as an alternative adjuvant. In 1994, a hepatitis A vaccine using the new adjuvant was licensed in Switzerland, and it was later approved for use in other countries the vaccine was well tolerated and highly immunogenic (SEDA-20,290) (SEDA-22,344). Nine people with a history of ocular sensitivity were immunized with hepatitis B, without untoward reactions. However, this result in such a small series should not be overestimated (75). There have been reports of three cases of inflammatory nodular reactions after hepatitis B immunization aluminium allergy was confirmed (76-78). 

This is an acute, non-invasive infectious disease associated with the upper respiratory tract (Chapter 7). The incubation period is from 2 to 5 days although the disease remains communicable for up to 4 weeks. A low molecular weight toxin is produced which affects myocardium, nervous and adrenal tissues. Death results in 3-5% of infected children. Diphtheria immunization protects by stimulating the production of an antitoxin. This antitoxin will protect against the disease but not against infection of the respiratory tract. The immunogen is a toxoid, prepared by formaldehyde treatment of the purified toxin (Chapter 23) and administered while adsorbed to an adjuvant, usually aluminium phosphate or aluminium hydroxide. The primary course of diphtheria prophylaxis consists of three doses starting at 2 months of age and separated by an interval of at least 1 month. The immune status of adults may be determined by administration of Schick test toxin, which is essentially a diluted form of the vaccine. 

Adsorption. The adsorption of the components of a vaccine on to a mineral adjuvant. The mineral adjuvants, or carriers, most often used are aluminium hydroxide and aluminium phosphate rarely calcium phosphate. Their effect is to increase the immunogenicity and decrease the toxicity, local and systemic, of a vaccine. Diphtheria vaccine, tetanus vaccine, diphtheria/tetanus vaccine and diphtheria/tetanus/pertussis (whole cell or acellular) vaccine, are generally prepared as adsorbed vaccines. 

MANCINO, D. OVARY, Z. (1980) Adjuvant effects of amorphous silica and of aluminium hydroxide on IgE and IgGl antibody production in different inbred mouse strains. International Archives of Allergy and Applied Immunology, 61, 253-258. 

Fig. (2). Adjuvant effect for stimulation of IgG Comparison of purified Quillaja saponaria saponins to other adjuvants. CD-I mice (5 per group) were immunized intradermaliy with lOpg cytochrome l>5 and the indicated adjuvant. The alum formulation consisted of 400 pg of aluminium hydroxide per dose. All saponins (QS-7, QS-17, QS-18, and QS-21) were used at 20 pg per dose. EIA titers were determined after two immunizations. The results are expressed as the mean of logio titers for individual mice per group. The error bar is 1 standard deviation. Reprinted from Kensil etal.,J. Immunol. 1991, 146 431-437, copyright 1991, with permission from The American Association of Immunologists.

Adjuvant a mixture of oils, emulsifiers, killed bacteria and other components, which serves to intensify unspecifically the immune response. The A., which is not (supposed to be) itself antigenic, is injected several times intramuscularly or subcutaneously into an animal to produce the maximal yield of antibodies. Freund s incomplete A., an emulsion of paraffin oils, protects the antigen from rapid degradation. Freund s complete A. contains in addition killed mycobacteria or tuberculosis bacteria. Both are used widely in experimental immunology. In vaccines, the A. is usually aluminium hydroxide or calcium phosphate gel. 

A phase I clinical study is in progress with healthy subjects receiving an AIDS vaccine in order to compare the adjuvants QS-21 and aluminium hydroxide. No significant side effects were observed in 100 healthy volunteers who received the QS-21 vaccine formulation. However no immunogenicity data are yet available for these formulations [14]. 

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