In vivo absorption of aluminium-containing vaccine adjuvants using 26Al

Flarend, Richard; Hem, Stanley L.; White, Joe L.; Elmore, D.; Suckow, Mark A.; Rudy, Anita; Dandashli, Euphemie A.

doi:10.1016/s0264-410x(97)00041-8

Cited by 176 publications

(111 citation statements)

References 7 publications

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“…It is expected that future comparative studies would be designed such that data could support selection of the right adjuvant. Novel adjuvants will be continually searched and evaluated, but their successes will be based on our further understanding of the interactions between human body and foreign microorganisms on a molecular level [460][461][462][463]. Ideally, such adjuvants would offer earlier, robust and durable immunity with less adverse events.…”

Section: Discussionmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Discussionmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…This finding is consistent with the presence of Alum in the circulation after its i.m. injection (47,48). This suggests that when coadministered, Alum and IL-36b may circulate, reach the liver, and synergistically transiently stimulate immune cells at distance.…”

Section: Discussionmentioning

confidence: 99%

IL-36–Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells

Palomo

Mastelic-Gavillet

Woldt

et al. 2016

The Journal of Immunology

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Human and mouse neonates exhibit limited vaccine responses characterized by predominant Th2 and limited Th1 responses. Because IL-36 exerts a synergic adjuvant effect with IL-12, enhancing Th1 polarization in adult (AD) mice, we administered IL-36β to neonatal (1-wk old) and AD control mice at the time of immunization with tetanus toxoid adsorbed to aluminum hydroxide (TT/Alum). Unexpectedly, the combination of IL-36β with TT/Alum, which was well tolerated in AD mice, proved toxic and even lethal in neonates. This neonatal toxicity was associated with high Il36r mRNA expression in neonatal liver, resulting in increased cytokine production. Liver Il36r mRNA expression decreased with the termination of fetal liver hematopoiesis, and this decrease correlated with a complete protection from TT/Alum/IL-36β–induced mortality. The combination of IL-36β and TT/Alum induced the rapid production of TNF-α and IFN-γ by liver myeloid and lymphoid cells, respectively. These responses were less marked when IL-36β was used alone, with no adverse effect. The toxicity of IL-36β + TT/Alum was abrogated by the administration of a neutralizing anti–TNF-α Ab, confirming causality. In conclusion, liver myeloid cells in neonatal mice are an important source of proinflammatory cytokines that may lead to TNF-α–mediated toxicity and even lethality.

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“…However, since initiation of adaptive immune responses takes place in lymphoid organs, antigens need to be translocated from the site of injection towards the local lymph node or the spleen, where interaction with adaptive T cells and B cells allows the completion of T-cell-dependent B-cell responses (Flarend et al, 1997). Itano et al (2003) describe this translocation of antigens in mice as two waves of antigen influx.…”

Section: Discussionmentioning

confidence: 99%

“…This may explain the activity of depot-type delivery systems such as W/O-based emulsions and aluminium. Flarend et al (1997) demonstrated that aluminium salts already start to dissolve within 1 hour of injection. Aluminium salts may maintain antigen at the site of injection for a relatively short, but sufficient, period of time.…”

Section: Discussionmentioning

confidence: 99%

Dose and timing requirements for immunogenicity of viral poultry vaccine antigen: investigations of emulsion-based depot function

Jansen¹,

Hofmans²,

Theelen³

et al. 2007

Avian Pathology

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The release requirements for vaccine antigens delivered by adjuvants with presumed depot function are poorly understood. Water-in-oil (W/O) emulsions are routinely used in many poultry vaccines. They strongly activate antibody production, and are regarded as a depot from which antigens are slowly released, resulting in prolonged antigen residence. However, from earlier studies we concluded that W/O adjuvant activity is partly based on the immunostimulatory activity of the oil phase. Here we assess the dose and regimen requirements for viral antigen in immunization experiments in chickens. Three-week-old to 4-week-old White Leghorn chickens were repeatedly injected with inactivated infectious bursal disease virus antigen over 48 days. Our aim was to compare the antibody responses in repeatedly injected animals, receiving fractioned doses of antigen, with the responses in animals receiving only one injection of the full dose of antigen formulated in either a W/O emulsion or in saline. We observed that repeated administration of small amounts of antigen results in a gradual increase of specific humoral immune responses during the immunization regimen. Immunization with a higher first dose evoked an early higher antibody response, which, however, reached a similar plateau level at the end of the regimen. When compared with lower firstdose regimens, a slow decline of serum antibody titre 2 weeks after the end of antigen injections indicated that repeated injection of small doses of antigen indeed mimics the efficacy of depot-forming adjuvants. All regimens of fractioned antigen in saline, however, proved less effective, when compared with a single-dose vaccination of the cumulative amount of antigen formulated in a W/O emulsion. From our data we confirm that W/O emulsions are very effective vaccine vehicles for improving antigen-specific humoral responses in chickens, owing to a combination of antigen residence-prolonging activity and direct immune stimulation.

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In vivo absorption of aluminium-containing vaccine adjuvants using 26Al

Cited by 176 publications

References 7 publications

Selection of Adjuvants for Enhanced Vaccine Potency

Selection of Adjuvants for Enhanced Vaccine Potency

IL-36–Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells

Dose and timing requirements for immunogenicity of viral poultry vaccine antigen: investigations of emulsion-based depot function

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