Effect of microenvironment pH of aluminum hydroxide adjuvant on the chemical stability of adsorbed antigen

Wittayanukulluk, Arunee; Jiang, Dongping; Regnier, Fred E.; Hem, Stanley L.

doi:10.1016/j.vaccine.2003.09.037

Cited by 59 publications

(56 citation statements)

References 10 publications

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“…It has been shown that the rate of acid-catalyzed hydrolysis of glucose-1-phosphate is significantly slower when the molecule is adsorbed to aluminum hydroxide adjuvant, increasing the effective pH of the environment by 2 pH units [56]. This effect would however also interfere with the human body's ability to break down the antigen from the vaccine, which may partially explain the heightened immune reaction.…”

Section: Aluminum and Mercury In Vaccinesmentioning

confidence: 99%

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Seneff

Davidson²,

Liu

2012

Entropy

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Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.

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Section: Aluminum and Mercury In Vaccinesmentioning

confidence: 99%

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Seneff

Davidson²,

Liu

2012

Entropy

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“…One possible cause for the protein instability is the different microenvironment pH on the aluminum particle surface. It has been shown that the surface of aluminum hydroxide is about 2 pH units higher than the bulk pH due to accumulation of hydroxyls on the particle surface [69]. Therefore, for a pH-sensitive antigen, the bulk pH needs to be adjusted lower than its optimal value to maximize its stability on the adjuvant surface.…”

Section: Stability Of Antigen With Aluminum Saltsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…As discussed above, Wittayanukulluk and coworkers (27) showed phosphate to be a modifying agent for aluminum oxyhydroxide, due to the effects of the ligand-exchange reaction, in addition to its role as a buffer. Furthermore, by modifying the physical nature of the aluminum oxyhydroxide, phosphate may also affect the potency of any vaccine when it is used as an adjuvant.…”

mentioning

confidence: 97%

“…Furthermore, removing a phosphate ion from solution and replacing it with a hydroxyl group has the potential to modify the pH of the formulation. Indeed, it has also been shown that the pH microenvironment adjacent to the aluminum oxyhydroxide particle surface is approximately 2 pH units higher than that of the surrounding solution (27). Since antigen binding occurs in a monolayer at the surface of the aluminum oxyhydroxide particle (22), the antigen will reside in this microenvironment and be subject to conditions different from those of the bulk solution.…”

mentioning

confidence: 99%

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

Watkinson

Soliakov

Ganesan³

et al. 2013

Clin Vaccine Immunol

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f Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for phosphate buffer in an anthrax vaccine (SparVax) containing recombinant protective antigen (rPA) and aluminum oxyhydroxide (AlOH) adjuvant (Alhydrogel). Phosphate ions bind to AlOH to produce an aluminum phosphate surface with a reduced rPA adsorption coefficient and binding capacity. However, these effects continued to increase as the free phosphate concentration increased, and the binding of rPA changed from endothermic to exothermic. Crucially, phosphate restored the thermostability of bound rPA so that it resembled the soluble form, even though it remained tightly bound to the surface. Batches of vaccine with either 0.25 mM (subsaturated) or 4 mM (saturated) phosphate were tested in a disease model at batch release, which showed that the latter was significantly more potent. Both formulations retained their potency for 3 years. The strongest aluminum adjuvant effects are thus likely to be via weakly attached or easily released native-state antigen proteins.

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Effect of microenvironment pH of aluminum hydroxide adjuvant on the chemical stability of adsorbed antigen

Cited by 59 publications

References 10 publications

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Selection of Adjuvants for Enhanced Vaccine Potency

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

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