Factors affecting alum–protein interactions

Huang, Min; Wang, Wei

doi:10.1016/j.ijpharm.2014.03.015

Cited by 36 publications

(30 citation statements)

References 35 publications

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“…Based on our results of AH RSP, 2 factors seemed to affect the catalysis of DiFMUP; the content of ligands available for ligand exchange (thiol and phosphate groups) 12 and antigen's molecular weight 34,59 by a steric effect, as reflected in the following ranking: TT (6 thiol groups,~150 kDa) > BSA (7 phospho-groups,~66 kDa) > b-Casein (5 phosphoserines,~26 kDa) > OVA (0-2 phosphoserines, 45 kDa). According to previous studies, several other factors can also affect the antigen's affinity for the sorbent surface, including the nature of the adjuvant (i.e., point of zero charge), 60 antigen conformation and IEP, 36 the adsorption mechanisms, 13 and the adsorption conditions (e.g., sodium chloride, 5 phosphate buffer, 23,54 and pH 61 ).…”

Section: Discussionmentioning

confidence: 91%

Mechanisms of Antigen Adsorption Onto an Aluminum-Hydroxide Adjuvant Evaluated by High-Throughput Screening

Jully

Mathot

Moniotte

et al. 2016

Journal of Pharmaceutical Sciences

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The adsorption mechanism of antigen on aluminum adjuvant can affect antigen elution at the injection site and hence the immune response. Our aim was to evaluate adsorption onto aluminum hydroxide (AH) by ligand exchange and electrostatic interactions of model proteins and antigens, bovine serum albumin (BSA), β-casein, ovalbumin (OVA), hepatitis B surface antigen, and tetanus toxin (TT). A high-throughput screening platform was developed to measure adsorption isotherms in the presence of electrolytes and ligand exchange by a fluorescence-spectroscopy method that detects the catalysis of 6,8-difluoro-4-methylumbelliferyl phosphate by free hydroxyl groups on AH. BSA adsorption depended on predominant electrostatic interactions. Ligand exchange contributes to the adsorption of β-casein, OVA, hepatitis B surface antigen, and TT onto AH. Based on relative surface phosphophilicity and adsorption isotherms in the presence of phosphate and fluoride, the capacities of the proteins to interact with AH by ligand exchange followed the trend: OVA < β-casein < BSA < TT. This could be explained by both the content of ligands available in the protein structure for ligand exchange and the antigen's molecular weight. The high-throughput screening platform can be used to better understand the contributions of ligand exchange and electrostatic attractions governing the interactions between an antigen adsorbed onto aluminum-containing adjuvant.

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Section: Discussionmentioning

confidence: 91%

Mechanisms of Antigen Adsorption Onto an Aluminum-Hydroxide Adjuvant Evaluated by High-Throughput Screening

Jully

Mathot

Moniotte

et al. 2016

Journal of Pharmaceutical Sciences

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“…Indeed, the authors revealed that formulations where strong attractive associations were present between vaccine components contained larger entities than those lacking these interactions when administered into biological fluid. Recent studies have also revealed that a small elevation in the particle size of the native adjuvant significantly impedes protein adsorption through a reduction in the adsorptive capacity of the material, although this has only been demonstrated using a single commercial preparation (Huang and Wang, 2014). A limitation of these studies, however, is the lack of data comparing the size of the antigen-complex with that of the adjuvant itself.…”

Section: Introductionmentioning

confidence: 99%

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering

2017

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The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>9 μm) and Alhydrogel® exhibited the smallest median size (2677 ± 120 nm) in comparison to Adju-Phos® or Imject alum® (7152 ± 308 and 7294 ± 146 nm respectively) despite its large polydispersity index (PDI). Dilution of these materials induced some degree of disaggregation within all samples with Adju-Phos® being the most significantly affected. The presence of BSA caused the median size of Alhydrogel® to increase but these trends were not evident when model vaccines were formulated with either Adju-Phos® or Imject alum®. Nevertheless, Alhydrogel® and Adju-Phos® exhibited comparable median sizes in the presence of this protein (4194 ± 466 and 4850 ± 501 nm respectively) with Imject alum® being considerably smaller (2155 ± 485 nm). These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site.

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“…Aluminum salts have a large surface area for antigen adsorption, and the adsorption of protein to Alum is generally fast and is reported to be complete within 5 min in certain cases. The adsorption of protein is mainly driven by electrostatic attraction or ligand exchange . The charged states of both the antigen and Alum, mostly determined by the solution pH, will influence the type of adsorption mechanism, although more than one type of mechanism may drive the interaction.…”

Section: Resultsmentioning

confidence: 99%

“…The adsorption of protein is mainly driven by electrostatic attraction or ligand exchange. 34,35 The charged states of both the antigen and Alum, mostly determined by the solution pH, will influence the type of adsorption mechanism, although more than one type of mechanism may drive the interaction. Figure 7 illustrates the effect of lysozyme and BSA adsorption on the surface charge of AlPO 4 .…”

Section: Effect Of Lysozyme and Bsamentioning

confidence: 99%

Investigation of the Sedimentation Behavior of Aluminum Phosphate: Influence of pH, Ionic Strength, and Model Antigens

Muthurania

Arunkumar

Jin

et al. 2015

Journal of Pharmaceutical Sciences

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Factors affecting alum–protein interactions

Cited by 36 publications

References 35 publications

Mechanisms of Antigen Adsorption Onto an Aluminum-Hydroxide Adjuvant Evaluated by High-Throughput Screening

Mechanisms of Antigen Adsorption Onto an Aluminum-Hydroxide Adjuvant Evaluated by High-Throughput Screening

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering

Investigation of the Sedimentation Behavior of Aluminum Phosphate: Influence of pH, Ionic Strength, and Model Antigens

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