Studies on the toxicities of aluminium hydroxide and calcium phosphate as immunological adjuvants for vaccines

Goto, Nobuichi; Katô, Hiroshi; Maeyama, Jun‐ichi; Eto, Komyo; Yoshihara, Shinobu

doi:10.1016/0264-410x(93)90377-a

Cited by 74 publications

(41 citation statements)

References 18 publications

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“…Other limitations of alum adjuvants are increased IgE production, allergenicity and neurotoxicity [8,[10][11][12]. Under conditions of reduced renal function, aluminium is accumulated in the body and becomes highly toxic causing fatal neurological syndrome and dialysis-associated dementia.…”

Section: Toxicity Of Alum-based Adjuvantsmentioning

confidence: 99%

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Petrovsky

2006

Vaccine

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Pure soluble, recombinant and synthetic antigens, despite their better tolerability, are unfortunately often much less immunogenic than live or killed whole organism vaccines. Thus, the move towards the development of safer subunit vaccines has created a major need for more potent adjuvants. In particular, there is an urgent need for adjuvants capable of boosting cellular (Th1) immunity but without unacceptable toxicity. The adjuvant activity of aluminium compounds (aluminium phosphate or hydroxide) was first described by Glenny and colleagues in 1926. Surprisingly, despite the description of over one hundred adjuvants in the scientific literature, alum remains the only adjuvant approved for human use in the USA. Unfortunately, alum has no effect on cellular immunity and is faced with increasing concerns regarding potential for cumulative aluminium toxicity. Why then has alum not been replaced in human vaccines? Despite the enormous number of candidates, potency has invariably been associated with increased toxicity, and this more than anything else has precluded their use, particularly in prophylactic vaccines where safety issues are paramount. Hence, there is a major unmet need for a safe efficacious adjuvant capable of boosting cellular plus humoral immunity. The extensive data on inulin-based adjuvants indicate that these are excellent candidates to replace alum as the adjuvant of choice for many vaccines. Particular advantages offered by inulin-based adjuvants is that they induce cellular in addition to humoral immunity and offer excellent safety, tolerability, ease of manufacture and formulation. Thus, adjuvants based on inulin have enormous potential for use in vaccines against both pathogens and cancer.

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Section: Toxicity Of Alum-based Adjuvantsmentioning

confidence: 99%

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Petrovsky

2006

Vaccine

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“…We have reported the in vitro toxic effects of Al and Ca (6). Ca-gel did not show any effect on vascular permeability, and lactate dehydrogenase release from macrophages or polymorphonuclear leukocytes, while its hemolytic activity on human and guinea pig erythrocytes was higher than that of Al-gel.…”

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confidence: 87%

Relationship between Hemolytic Activity and Adsorption Capacity of Aluminum Hydroxide and Calcium Phosphate as Immunological Adjuvants for Biologicals

Katô

Shibano

Saito

et al. 1994

Microbiology and Immunology

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Aluminum hydroxide (Al) and calcium phosphate (Ca) gels have been used as vaccine adjuvants for many years. We investigated mechanism of the hemolytic activities of both adjuvant materials. The hemolytic activity of each gel depended on the gel dose. The adsorption capacities and the hemolytic activities of both adjuvants decreased as the concentration of phosphate increased in a gel-washing solution. A positive correlation between the hemolytic activity and the adsorption capacity was found in Al-gel. A disruptive effect of Ca-gel on membrane of erythrocytes was shown by electron microscopy. Ca-gel required more than 10 times as much pre-adsorbed ovalbumin as did Al-gel to inhibit the hemolysis. These results suggest that the hemolytic activity of both adjuvant materials depended mainly on the adsorption ability, and it may be useful to control the adsorption ability of adjuvants to reduce their hemolytic activity.

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“…Hence, a major challenge in adjuvant development is how to achieve a potent adjuvant effect while avoiding reactogenicity or toxicity [27]. All the previously described candidate human adjuvants, including alum [28], MF59 [29], "Ideally, adjuvants should strongly stimulate B-and T-cell immunity while avoiding the excess innate immune system activation and inflammatory cytokine production that mediates adjuvant reactogenicity. "…”

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confidence: 99%

Freeing vaccine adjuvants from dangerous immunological dogma

Petrovsky¹

2008

Expert Review of Vaccines

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Studies on the toxicities of aluminium hydroxide and calcium phosphate as immunological adjuvants for vaccines

Cited by 74 publications

References 18 publications

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Relationship between Hemolytic Activity and Adsorption Capacity of Aluminum Hydroxide and Calcium Phosphate as Immunological Adjuvants for Biologicals

Freeing vaccine adjuvants from dangerous immunological dogma

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