Aluminum phosphate adjuvant

Aluminum hydroxyphosphate aluminium hydroxyphosphate Adju-Phos Rehydraphos. 

The molecular weight is dependent on the degree of substitution of phosphate groups for hydroxyl groups. 

Aluminum phosphate adjuvant is not a stoichiometric compound. Rather, the degree of phosphate group substitution for hydroxyl groups depends on the precipitation recipe and conditions. 

Aluminum phosphate adjuvant is used in parenteral human and veterinary vaccines. It activates Th2 immune responses, including IgG and IgE antibody responses. 

Aluminum phosphate adjuvant is a white hydrogel that sediments slowly and forms a clear supernatant. 

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A dose of vaccine containing ILf (2-2.5 pg) tetanus toxoid in aluminum phosphate adjuvant at pH 6.0 (1 1) (TT j) or a dose of adjuvant alone in a dose corresponding to the dose given with the vaccine (ADJ) is administered intramuscularly. The administration site is the left hind leg quadriceps see Note 11). 

Regnstrom, K., Ragnarsson, E.G.E., Rydell, N., Sjoholm, I., and Artursson, P. (2002) Tetanus antigen modulates the gene expression profile of aluminum phosphate adjuvant in spleen lymphocytes in vivo. Pharmacogenomics J. 2, 57-64. 

Aluminum phosphate adjuvant is stable for at least six months when stored at 4-30°C in well-sealed inert containers. It must not be allowed to freeze as the hydrated colloid structure will be irreversibly damaged. 

Aluminum phosphate adjuvant is formed by the reaction of a solution of aluminum chloride and phosphoric acid with alkali hydroxide. 

Very often, vaccines are formulated with certain substances to enhance the immune response. These substances are called adjuvants (from the Latin adju-vare, which means to help ). The most common adjuvants for human use are aluminum hydroxide, aluminum phosphate, and calcium phosphate. Other adjuvants being used include bacteria and cholesterol. Mineral oil emulsions are normally the adjuvants used in animal studies. The adjuvant known as Freund s complete adjuvant consists of killed tubercle bacilli in water-inmineral oil emulsion, and Freund s incomplete adjuvant is a water-in-oil emulsion. Both these adjuvants are effective in stimulating an immune response, but they cause unacceptable side effects in humans (see Table 4.2). 

Following intramuscular administration of aluminum hydroxide or aluminum phosphate vaccine adjuvants in rabbits, increased levels of26Al were found in the kidney, spleen, liver, heart, lymph nodes, and brain (in decreasing order of aluminum concentration) (Flarend et al. 1997). 

The commonly recognized adjuvants are remarkable for their diversities. Soluble immunogens can be adsorbed onto the following kinds of inorganic suspensions alumina cream, aluminum phosphate, and aluminum sulfate. Adsorption onto organic carriers such as blood, charcoal, calcium alginate, or polyacrylamide gels has also enhanced responses. A Maalox... 

Aluminum, in the form of aluminum hydroxide, aluminum phosphate or aluminum potassium sulfate, is used as adjuvant in various vaccine formulations to elicit an increased immunogenic response. 

Aluminum adjuvants in human vaccines are either aluminum hydroxyphosphate (commonly referred to as aluminum phosphate) or aluminum oxyhydroxide (aluminum hydroxide). Aluminum-based vaccines are prepared by adsorption of antigen to commercial aluminum hydroxide or aluminum phosphate gels or by mixing antigen with alum (potassium aluminum sulfate),... 

When exposed to phosphate, carbonate, sulfate, or borate anions, the point of zero charge for aluminum hydroxide adjuvant decreases. 

The USP 28 monograph for aluminum phosphate (ALPO4) gel describes aluminum phosphate, which is used as an antacid, not as a vaccine adjuvant. 

Kreuter and Speiser [77] developed a dispersion polymerization producing adjuvant nanospheres of polymethylmethacrylate) (PMMA). The monomer is dissolved in phosphate buffered saline and initiated by gamma radiation in the presence and absence of influenza virions. These systems showed enhanced adjuvant effect over aluminum hydroxide and prolonged antibody response. PMMA particles could be distinguished by TEM studies and the particle size was reported elsewhere to be 130 nm by photon correlation spectroscopy [75], The particle size could be reduced, producing monodisperse particles by inclusion of protective colloids, such as proteins or casein [40], Poly(methylmethacrylate) nanoparticles are also prepared... 

A wide variety of materials have been explored for their adjuvant activity, although not all are equally effective or nontoxic, especially in humans. Alum and other aluminum salts were first recognized in 1926 and remain the most effective agents licensed for human use by the FDA, although some French products also use calcium phosphate. However, in recent years it has become evident that new and improved vaccine adjuvants are needed. 

Kato H, Shibano M, Saito T, et al. 1994. Relationship between hemolytic activity and adsorption capacity of aluminum hydroxide and calcium phosphate as immunological adjuvants for biologicals. Microbiol Immunol 38 543-548. 

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