Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties

Goto, Nobuichi; Katô, Hiroshi; Maeyama, Jun‐ichi; Shibano, Michiko; Saito, Takuya; Yamaguchi, Junji; Yoshihara, Shinobu

doi:10.1016/s0264-410x(97)00054-6

Cited by 122 publications

(67 citation statements)

References 16 publications

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“…Indeed, we could monitor the recruitment in the muscle of CD11bϩ and MHC class IIϩ blood cells 4 days after administration of all adjuvants. These data are in agreement with previous reports showing that the injection of alum results in local inflammation (12,13) and with more recent data showing that alum induced monocyte recruitment in the peritoneum (14). Furthermore, two of the adjuvant core response genes identified in mouse muscle, CCL2 and IL1b, were also up-regulated in the peritoneum after alum injection (14).…”

Section: Discussionsupporting

confidence: 93%

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Molecular and cellular signatures of human vaccine adjuvants

Mosca

Tritto

Muzzi

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

443

335

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Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b؉ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.innate immunity ͉ microarray ͉ MF59 ͉ alum ͉ CpG ͉ oligonucleotide

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Section: Discussionsupporting

confidence: 93%

“…Alum i.m. administration resulted in cell recruitment events at the injection site (12,13). More recently, it has been demonstrated that i.p.…”

mentioning

confidence: 99%

Molecular and cellular signatures of human vaccine adjuvants

Mosca

Tritto

Muzzi

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

443

335

View full text Add to dashboard Cite

show abstract

“…They postulated that this was probably due to the fact that the CAP nanoparticles are not recognized by the inflammatory cells due to their smaller size. On the other hand the present study did not agree with what mentioned [34] that tissue reactions caused by injection of CAP adjuvant completely ceased by the 4th week, while irritation caused by alum persisted till 8 weeks.…”

Section: Discussioncontrasting

confidence: 99%

“…The experimental time durations were chosen according to [15] who reported that the irritation caused by an aluminum hydroxide gel and suspension persisted for 8 weeks, while the local tissue reactions caused by the injection of CAP gel and suspension completely ceased by the 4th week. Thus, the present study continued for 9 weeks post immunization in case of alum adjuvanted vaccine and 5 weeks in case of CAP adjuvanted vaccine and the samples were collected weekly.…”

Section: F Study Designmentioning

confidence: 99%

Evaluation of the Effects of Aluminum Phosphate and Calcium Phosphate Nanoparticles as Adjuvants in Vaccinated Mice

Issa¹,

Salim²,

Zidan³

et al. 2014

IJCEA

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Abstract-The present study aim at studying the histological effects of both aluminum phosphate (Alum) and calcium phosphate (CAP) nanoparticles adjuvant in parallel with their potentials as adjuvant and the related immune response to tetanus toxoid vaccine adsorbed on both of them. Ninety Swiss albino mice were used in the experiment (50% adults and 50% juveniles). Mice were immunized intramuscularly with 0.125 ml adjuvanted tetanus toxoid vaccine. For alum adjuvant study, 27 adult mice and 27 juvenile ones were injected with alum adjuvanted vaccine and sacrificed weekly as triplects for 9 weeks. For calcium phosphate adjuvant study, 15 adult mice and 15 juvenile ones were injected with calcium phosphate adjuvanted vaccine and sacrificed weekly as triplects for 5 weeks. The effect of alum and calcium phosphate nanoparticles adjuvants in enhancing the immune response of tetanus toxoid vaccine were monitored through measurement of antibody titer in sera of mice. The pathological effect of both adjuvants were monitored through histological study of liver, brain, kidney and injected muscle of sacrificed animals. Recorded data revealed that both adjuvanted vaccine caused histopathological changes in tissues of liver, kidney, brain and injected muscle. On the other hand alum adjuvanted tetanus toxoid vaccine was more potent and showed higher antibody level than CAP adjuvanted vaccines.

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“…A significant amount of data has accumulated demonstrating that alum also has immunostimulatory activities. It is well known that alum injection results in cell recruitment to the injection site [7,8]. More recently, it was reported that alum activates human monocytes and macrophages in vitro [9][10][11][12].…”

Section: Proposed Mechanisms Of Action For Alummentioning

confidence: 99%

Alum adjuvanticity: Unraveling a century old mystery

2008

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The development of vaccine adjuvants for human use has been one of the slowest processes in the history of medicine. For almost one century, aluminium hydroxide (alum) has been the only vaccine adjuvant approved worldwide. Only in the past decade have two oil-inwater emulsions and one TLR agonist been approved by the European authorities as new vaccine adjuvants. Despite the fact that alum has been injected into billions of people, its mechanism of action is not fully understood. Recently, several reports have greatly increased our knowledge of the molecular and cellular events triggered by alum; however, the contribution of each of these processes to alum adjuvanticity is still unclear. A study published in this issue of the European Journal of Immunology, together with two recent publications, have demonstrated that the NOD-like receptor, pyrin domain containing 3 (Nlrp3)-inflammasome is the molecular target of alum immunostimulatory activity in vitro. Surprisingly, these three studies reported conflicting results on the requirement of the Nlrp3 inflammasome complex for alum adjuvant effects in vivo. This commentary attempts to resolve some of these discrepancies.

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Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties

Cited by 122 publications

References 16 publications

Molecular and cellular signatures of human vaccine adjuvants

Molecular and cellular signatures of human vaccine adjuvants

Evaluation of the Effects of Aluminum Phosphate and Calcium Phosphate Nanoparticles as Adjuvants in Vaccinated Mice

Alum adjuvanticity: Unraveling a century old mystery

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