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Insight of Aluminum Salt Adjuvants

Traditional vaccines consisted of deactivated pathogen such as bacterium or virus.Modern vaccines are much more refined as they consist of specific toxoids or proteins isolated from the pathogen.This has reduced reactogenicity, which is linked to lower immunogenicity.1Adjuvants are frequently used for enhancing the antigenic properties and immunogenicity of such antigens..

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Insight of Aluminum Salt Adjuvants

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    1. Insight of Aluminum Salt Adjuvants 1

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    3. Aluminum salts are the most widely used adjuvants for human and animal vaccines. The immunogenic properties were first discovered in 1926.1 Two of the most commonly used aluminum adjuvants are: AlOOH – Aluminum Oxyhydroxide AlPO4 – Aluminum Phosphate The adjuvant of choice is based on the compatibility with the antigen. Aluminum Based Adjuvants 3

    4. The following slides will focus on characterization of AlOOH and AlPO4 adjuvants. This is based on measurement and information obtained from various analytical techniques:1 Characterization of Aluminum Adjuvants 4

    5. The position and width of diffraction can used for identifying the atomic arrangement and crystallinity of the analyte. X-ray Diffraction 1 5

    6. Aluminum hydroxide has fibrous morphology, a characteristic of boehmite crystalline structures. AlPO4 shows up as network of platy particles. Transmission Electron Microscopy 6

    7. Uses vibration to determine the functional groups and properties of the analyte Infrared Spectroscopy 7

    8. Energy Dispersive spectrometry spectrum shows peaks that are related to the energy characteristics of an element. For aluminum hydroxide, only presence of aluminum is detected; whereas for aluminum phosphate, presence of aluminum and phosphorus is detected. 1 Doppler Electrophoretic Light Scattering Analysis can be used to determine the isoelectric point (pI) of the analyte as a function of pH. Aluminum hydroxide, the pI was determined to be at 11. Hence at physiological pH of 7.4, the surface is positively charged. 1 Aluminum phosphate, has pI ranging between 5-7. Therefore at physiolgical pH, the surface has a negative charge. 1 Solubility in interstitial fluid was tested by dissolving the adjuvant in presence of citric, lactic and malic acids. Use of citrate concentration of 270 mEq/L at physiological temperature of 37°C resulted in 9% dissolution of AlOOH and 100% for AlPO4. 1 Other Methods: 8

    9. AlOOH has greater affinity to ligand with acidic pI than basic pI.* Albumin (pI = 4.8) is able to absorb better than lysozyme (pI = 11.0). Mechanism of attraction is electrostatic binding. Surface charge of AlOOH can be altered with presence of phosphate anions in the buffer. Phosphate deposits on the surface decreases the pI of AlOOH.1 The phosphate ligand exchange also allows for stronger binding of proteins with high phosphate content. Adsorption Isotherm (AlOOH) 9 Adsorption measurement include the ligand adsorption capacity and affinity. Affinity is characterized as adsorption coefficient. Ligands with greater affinity are able to displace those with less affinity. Attractive electrostatic forces are the primary mechanism for adsorption, hence ligand of opposite charge will have the greatest affinity. Adsorption measurement include the ligand adsorption capacity and affinity. Affinity is characterized as adsorption coefficient. Ligands with greater affinity are able to displace those with less affinity. Attractive electrostatic forces are the primary mechanism for adsorption, hence ligand of opposite charge will have the greatest affinity.

    10. Three different species of Streptococcus Pneumoniae antigen was used for analyzing the effects of ionic strength of the buffer on the adsorption capacity. Ionic strength of the buffer is increased as [NaCl] in the buffer is increased from 0.06 M to 0.25 M and 0.75 M.1 10 Adsorption Isotherm (AlOOH)

    11. AlPO4 has greater affinity for ligands with basic pI than acidic pI.* Lysozyme (pI = 11.0) is better able to adsorb than albumin (pI = 4.8). pI of AlPO4 can be changed. 11 Adsorption Isotherm (AlPO4)

    12. Changes occur in the protein upon adsorption to the adjuvant: Decrease in melting temperature ( Lyszoyme) 1 Change in contribution by different transitions (Ovalbumin) 1 These changes are irreversible. 1 In conclusion, adsorption of protein onto adjuvant leads to reduced thermal stability of the protein. 12 Effects of aluminum adjuvant on thermal stability of protein antigens (Differnetial Scanning Calorimetry)

    13. Changes observed upon adsorption to the adjuvant: Change in secondary structure upon adsorption to the adjuvant. 1 Protein is more prone to aggregation when it is adsorbed to an adjuvant. 1 In conclusion, secondary structure are more stable for in-solution proteins. Structural changes that occur upon adsorption to the aluminum adjuvant can possibly make the protein more prone to aggregation. 1 13 Effects of aluminum adjuvant on secondary structures of protein antigens (FTIR Spectroscopy)

    14. Depot Effect and Antigen Delivery Adjuvants form small depots that attract macrophages and enhance the immune response. 1 Slow, elongated release of the antigen prolongs the delivery of the antigen to APC and lymphocytes. 1 Adjuvants enhance the antigen interaction with antigen presenting cells (APC) by modifying the conformation of the antigen to make it more compatible for phagocytosis. 1 Adjuvants trigger production of eosinophils which leads to increased inflammatory response as wells as greater antibody response. 1 14 Mechanism of action of aluminum salts (Immunology)

    15. Aluminum oxyhydroxide and aluminum phosphate have very opposite chemical characteristics and this allows the use of aluminum salts in wide variety of antigens. Certain properties of the salt can be altered based on the factors such as pH during formulation. Upon adsorption, aluminum oxyhydroxide and aluminum phosphate cause change in conformation, secondary structure and thermal stability of the protein. Aluminum adjuvants are able to increase immune response by depot effect, enhancing phagocytosis and increasing inflammatory response. 15 Conclusion

    16. Over billion dosage of aluminum adjuvant vaccines have been administered through the globe! Some of the current vaccines are: 1 Diphtheria vaccine – Daptacel (AlPO4-sulfate), Infanrix (AlOOH) Pneumococcal – Prevnar (AlPO4) Human Papillomavirus - Gardasil (AlOOH) Hepatitis A – Vaqta (AlOOH-sulfate), Havrix (AlOOH) Hepatitis B –, Engerix-B (AlOOH and AlPO4 hybrid) Anthrax - BioThrax (AlOOH) 16 Aluminum salts as adjuvants in current vaccines http://explorevaccines.wordpress.com/2008/11/06/aluminum-in-vaccines-part-1/ http://explorevaccines.wordpress.com/2008/11/06/aluminum-in-vaccines-part-1/

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