Relationship between physical and chemical properties of aluminum-containing adjuvants and immunopotentiation

Aluminum-containing adjuvants are an important component of many vaccines because they safely potentiate the immune response. The structure and properties of aluminum hydroxide adjuvant, aluminum phosphate adjuvant and alum-precipitated adjuvants are presented in this review. The major antigen adsorption mechanisms, electrostatic attraction and ligand exchange, are related to the adjuvant structure. The manner by which aluminum-containing adjuvants potentiate the immune response is related to the structure, properties of the adjuvant and adsorption mechanism. Immunopotentiation occurs through the following sequential steps: inflammation and recruitment of antigen-presenting cells, retention of antigen at the injection site, uptake of antigen, dendritic cell maturation, T-cell activation and T-cell differentiation.

[1]  S. Hem,et al.  Relationship of adsorption mechanism of antigens by aluminum-containing adjuvants to in vitro elution in interstitial fluid. , 2006, Vaccine.

[2]  F. Regnier,et al.  The in vitro displacement of adsorbed model antigens from aluminium-containing adjuvants by interstitial proteins. , 1999, Vaccine.

[3]  J. White,et al.  Solubilization of aluminum-containing adjuvants by constituents of interstitial fluid. , 1991, Journal of parenteral science and technology : a publication of the Parenteral Drug Association.

[4]  Stephen Shaw,et al.  Lymph-Borne Chemokines and Other Low Molecular Weight Molecules Reach High Endothelial Venules via Specialized Conduits While a Functional Barrier Limits Access to the Lymphocyte Microenvironments in Lymph Node Cortex , 2000, The Journal of experimental medicine.

[5]  H. HogenEsch,et al.  Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants. , 2007, Vaccine.

[6]  A. T. Glenny,et al.  Immunological notes. XVII–XXIV , 1926 .

[7]  J. Paul Robinson,et al.  Role of aluminum-containing adjuvants in antigen internalization by dendritic cells in vitro. , 2005, Vaccine.

[8]  S. Akira,et al.  A Toll-like receptor recognizes bacterial DNA , 2000, Nature.

[9]  S. Hem,et al.  Aluminum Compounds Used as Adjuvants in Vaccines , 1990, Pharmaceutical Research.

[10]  R. Gupta,et al.  In vivo distribution of radioactivity in mice after injection of biodegradable polymer microspheres containing 14C-labeled tetanus toxoid. , 1996, Vaccine.

[11]  L. Holt Developments in Diphtheria Prophylaxis. , 1950 .

[12]  A. Kara,et al.  Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b‐CRM197 conjugate vaccine , 2003, Pediatrics international : official journal of the Japan Pediatric Society.

[13]  M. Bianchi DAMPs, PAMPs and alarmins: all we need to know about danger , 2007, Journal of leukocyte biology.

[14]  Xu Liu,et al.  Adjuvant synergy in the response to hepatitis B vaccines. , 2003, Vaccine.

[15]  L. Peek,et al.  Effects of stabilizers on the destabilization of proteins upon adsorption to aluminum salt adjuvants. , 2007, Journal of pharmaceutical sciences.

[16]  R. Geahlen,et al.  Effect of phosphorylation of ovalbumin on adsorption by aluminum-containing adjuvants and elution upon exposure to interstitial fluid. , 2005, Vaccine.

[17]  J. F. Young,et al.  Induction of protective class I MHC-restricted CTL in mice by a recombinant influenza vaccine in aluminium hydroxide adjuvant. , 1992, Vaccine.

[18]  G. Zlabinger,et al.  Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation. , 1985, Clinical and experimental immunology.

[19]  Brigitte Colau,et al.  Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. , 2006, Vaccine.

[20]  F. Re,et al.  Aluminum Hydroxide Adjuvants Activate Caspase-1 and Induce IL-1β and IL-18 Release1 , 2007, The Journal of Immunology.

[21]  Anna Sokolovska,et al.  Relationship between the strength of antigen adsorption to an aluminum-containing adjuvant and the immune response. , 2007, Vaccine.

[22]  M. Suckow,et al.  In vivo absorption of aluminium-containing vaccine adjuvants using 26Al. , 1997, Vaccine.

[23]  J. White,et al.  Stability of aluminium-containing adjuvants during aging at room temperature. , 2000, Vaccine.

[24]  H. Grey,et al.  Antigen processing and presentation to T cells. , 1985, Immunology today.

[25]  S. Goldberg,et al.  Chemistry of the Solid-Water Interface Processes at the Mineral-Water and Particle-Water Interface in Natural Systems , 1993 .

[26]  R. Walls Eosinophil Response to Alum Adjuvants: Involvement of T Cells in Non-Antigen-Dependent Mechanisms 1 , 1977, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[27]  R. Steinman,et al.  Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. , 1999, Immunity.

[28]  S. Hem,et al.  Effect of Anions on Model Aluminum-Adjuvant-Containing Vaccines , 1995 .

[29]  R. Sitrin,et al.  Surface phosphophilicity of aluminum-containing adjuvants probed by their efficiency for catalyzing the P--O bond cleavage with chromogenic and fluorogenic substrates. , 2001, Analytical biochemistry.

[30]  R. Schirmbeck,et al.  Codelivery of a DNA vaccine and a protein vaccine with aluminum phosphate stimulates a potent and multivalent immune response , 2003, Journal of Molecular Medicine.

[31]  J. Eldridge,et al.  Effect of monophosphoryl lipid A (MPL) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM197 conjugate vaccine in healthy toddlers. , 2002, Vaccine.

[32]  N. Goto,et al.  Histopathological Studies of Reactions in Mice Injected with Aluminum‐Adsorbed Tetanus Toxoid , 1982, Microbiology and immunology.

[33]  N. Goto,et al.  Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties. , 1997, Vaccine.

[34]  M. Ulanova,et al.  The Common Vaccine Adjuvant Aluminum Hydroxide Up-Regulates Accessory Properties of Human Monocytes via an Interleukin-4-Dependent Mechanism , 2001, Infection and Immunity.

[35]  B. Beutler,et al.  Adjuvant-Enhanced Antibody Responses in the Absence of Toll-Like Receptor Signaling , 2006, Science.

[36]  S. Hem,et al.  Relationship between the degree of antigen adsorption to aluminum hydroxide adjuvant in interstitial fluid and antibody production. , 2003, Vaccine.

[37]  S. Akira,et al.  Toll-like receptors control activation of adaptive immune responses , 2001, Nature Immunology.

[38]  J. Paul Robinson,et al.  Distribution of adsorbed antigen in mono-valent and combination vaccines. , 2004, Vaccine.

[39]  P. van Damme,et al.  Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system. , 1998, Vaccine.

[40]  J. Vadolas,et al.  The role of macrophages in the induction and regulation of immunity elicited by exogenous antigens , 1998, European journal of immunology.

[41]  J. White,et al.  Stability of aluminium-containing adjuvants to autoclaving. , 1999, Vaccine.

[42]  R. K. Evans,et al.  Enhanced type I immune response to a hepatitis B DNA vaccine by formulation with calcium- or aluminum phosphate. , 2000, Vaccine.

[43]  Ruslan Medzhitov,et al.  Control of adaptive immune responses by Toll-like receptors. , 2002, Current opinion in immunology.

[44]  F. Martinon,et al.  New insights into the mechanism of IL-1β maturation , 2003 .

[45]  Dexiang Chen,et al.  Stabilization of alum-adjuvanted vaccine dry powder formulations: mechanism and application. , 2003, Journal of pharmaceutical sciences.

[46]  L. Peek,et al.  Effects of Adsorption to Aluminum Salt Adjuvants on the Structure and Stability of Model Protein Antigens* , 2005, Journal of Biological Chemistry.

[47]  L. Peek,et al.  A systematic approach to stabilizing EBA-175 RII-NG for use as a malaria vaccine. , 2006, Vaccine.

[48]  A. Lanzavecchia,et al.  Mechanisms of antigen uptake for presentation. , 1996, Current opinion in immunology.

[49]  A. Glenny,et al.  Rate of Disappearance of Diphtheria Toxoid injected into Rabbits and Guinea-Pigs: Toxoid precipitated with Alum. , 1931 .

[50]  A. Krieg,et al.  CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. , 1998, Journal of immunology.

[51]  S. Durham,et al.  Aluminium hydroxide down‐regulates T helper 2 responses by allergen‐stimulated human peripheral blood mononuclear cells , 2004, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[52]  J. D. Robertson,et al.  Monitoring the Retention of a Protein Antigen in Complete Freund's Adjuvant, Alum, and Pluronic F-127 Gel Formulations by X-ray Fluorescence , 2001, Pharmaceutical development and technology.

[53]  L. Peek,et al.  A rapid, three-step process for the preformulation of a recombinant ricin toxin A-chain vaccine. , 2007, Journal of pharmaceutical sciences.

[54]  S. Giardina,et al.  Evaluation of the compatibility of a second generation recombinant anthrax vaccine with aluminum-containing adjuvants. , 2003, Vaccine.

[55]  F. Regnier,et al.  Effect of microenvironment pH of aluminum hydroxide adjuvant on the chemical stability of adsorbed antigen. , 2004, Vaccine.

[56]  Thomas C. Mitchell,et al.  The Vaccine Adjuvant Monophosphoryl Lipid A as a TRIF-Biased Agonist of TLR4 , 2007, Science.

[57]  H. HogenEsch,et al.  Activation of dendritic cells and induction of CD4(+) T cell differentiation by aluminum-containing adjuvants. , 2007, Vaccine.

[58]  F. Regnier,et al.  Contribution of electrostatic and hydrophobic interactions to the adsorption of proteins by aluminium-containing adjuvants. , 1995, Vaccine.

[59]  C. Mackay,et al.  Homing of naive, memory and effector lymphocytes. , 1993, Current opinion in immunology.

[60]  S. Hem,et al.  Effect of the Degree of Phosphate Substitution in Aluminum Hydroxide Adjuvant on the Adsorption of Phosphorylated Proteins , 2003, Pharmaceutical development and technology.

[61]  Formulation of botulinum neurotoxin heavy chain fragments for vaccine development: mechanisms of adsorption to an aluminum-containing adjuvant. , 2005, Vaccine.

[62]  C. Michelet-Habchi,et al.  Aluminium assay and evaluation of the local reaction at several time points after intramuscular administration of aluminium containing vaccines in the Cynomolgus monkey. , 2005, Vaccine.

[63]  White,et al.  Effect of pH on the Elution of Model Antigens from Aluminum-Containing Adjuvants. , 1998, Journal of colloid and interface science.

[64]  P. Kalinski,et al.  T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. , 1999, Immunology today.

[65]  M. Ameri,et al.  Optimization of an Alum-Adsorbed Vaccine Powder Formulation for Epidermal Powder Immunization , 2003, Pharmaceutical Research.

[66]  J. Arciniega,et al.  Immunogenicity in mice of anthrax recombinant protective antigen in the presence of aluminum adjuvants. , 2005, Vaccine.

[67]  D. Dormont,et al.  Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type. , 2004, Vaccine.

[68]  H. HogenEsch,et al.  Mechanisms of stimulation of the immune response by aluminum adjuvants. , 2002, Vaccine.

[69]  B. Kerwin,et al.  Secondary structures of proteins adsorbed onto aluminum hydroxide: infrared spectroscopic analysis of proteins from low solution concentrations. , 2006, Analytical biochemistry.

[70]  S. Hem,et al.  Mechanism of adsorption of hepatitis B surface antigen by aluminum hydroxide adjuvant. , 2004, Vaccine.

[71]  R. White,et al.  Studies on antibody production. III. The alum granuloma. , 1955 .

[72]  N. Sheikh,et al.  Generation of antigen specific CD8+ cytotoxic T cells following immunization with soluble protein formulated with novel glycoside adjuvants. , 1999, Vaccine.

[73]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[74]  A. Khoruts,et al.  Visualizing the generation of memory CD4 T cells in the whole body , 2001, Nature.

[75]  C. Johnston,et al.  Measuring the surface area of aluminum hydroxide adjuvant. , 2002, Journal of pharmaceutical sciences.

[76]  A. Sher,et al.  Adsorption to aluminum hydroxide promotes the activity of IL-12 as an adjuvant for antibody as well as type 1 cytokine responses to HIV-1 gp120. , 1997, Journal of immunology.

[77]  C. Johnston,et al.  Using Rate of Acid Neutralization to Characterize Aluminum Phosphate Adjuvant , 2003, Pharmaceutical development and technology.

[78]  J. White,et al.  Predicting the adsorption of proteins by aluminium-containing adjuvants. , 1991, Vaccine.

[79]  R. K. Evans,et al.  Enhancement of DNA vaccine potency using conventional aluminum adjuvants. , 1999, Vaccine.