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Vaccines With Aluminum-containing Adjuvants: Optimizing Vaccine Efficacy And Thermal Stability.
Tanya Clapp, P. Siebert, D. Chen, LaToya Jones Braun
Published 2011 · Chemistry, Medicine
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Aluminum-containing adjuvants have been used to enhance the immune response against killed, inactivated, and subunit antigens for more than seven decades. Nevertheless, we are only beginning to gain important insight as to what may be some very fundamental parameters for optimizing their use. For example, there is evidence that the conventional approach of maximizing antigen binding (amount and/or strength) may not result in an optimal immune response. Adsorption of antigen onto the adjuvant has recently been suggested to decrease the thermal stability of some antigens; however, whether adsorption-induced alterations to the structure and/or stability of the antigen have consequences for the elicited immune response is unclear. Finally, the thermal stability of vaccines with aluminum-containing adjuvants is not robust. Optimizing the stability of these vaccines requires an understanding of the freeze sensitivity of the adjuvant, freeze and heat sensitivity of the antigen in the presence of the adjuvant, and perhaps most important, how (or whether) various approaches to formulation can be used to address these instabilities. This review attempts to summarize recent findings regarding issues that may dictate the success of vaccines with aluminum-containing adjuvants.
This paper references
Stabilization of alum-adjuvanted vaccine dry powder formulations: mechanism and application.
Y. Maa (2003)
Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
S. Eisenbarth (2008)
Predicting the adsorption of proteins by aluminium-containing adjuvants.
S. Seeber (1991)
Protection of aluminum hydroxide during lyophilisation as an adjuvant for freeze-dried vaccines
L. Wolff (2008)
Cutting Edge: Necrosis Activates the NLRP3 Inflammasome1
H. Li (2009)
Secondary structure analysis of HIV-1-gp41 in solution and adsorbed to aluminum hydroxide by Fourier transform infrared spectroscopy.
A. Agopian (2007)
Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids
S. Cape (2008)
Stability of a trivalent recombinant protein vaccine formulation against botulinum neurotoxin during storage in aqueous solution.
C. Vessely (2009)
Association Between Immunogenicity and Adsorption of a Recombinant Streptococcus pneumoniae Vaccine Antigen by an Aluminum Adjuvant
Philip M Levesque (2006)
Secondary structures of proteins adsorbed onto aluminum hydroxide: infrared spectroscopic analysis of proteins from low solution concentrations.
A. Dong (2006)
Effect of pH and ionic strength on the physical stability of adenovirus type 5.
J. Rexroad (2006)
Effect of phosphorylation of ovalbumin on adsorption by aluminum-containing adjuvants and elution upon exposure to interstitial fluid.
Garry L. Morefield (2005)
Near-critical fluid micronization of stabilized vaccines, antibiotics and anti-virals
R. Sievers (2007)
Contribution of electrostatic and hydrophobic interactions to the adsorption of proteins by aluminium-containing adjuvants.
R. al-Shakhshir (1995)
Evidence for the denaturation of recombinant hepatitis B surface antigen on aluminium hydroxide gel.
D. Tleugabulova (1998)
The in vitro displacement of adsorbed model antigens from aluminium-containing adjuvants by interstitial proteins.
J. Heimlich (1999)
Treatment of aluminium hydroxide adjuvant to optimize the adsorption of basic proteins.
J. V. Rinella (1996)
High-throughput screening of stabilizers for Respiratory Syncytial Virus: Identification of stabilizers and their effects on the conformational thermostability of viral particles
S. Ausar (2007)
Considerable Differences in Vaccine Immunogenicities and Efficacies Related to the Diluent Used for Aluminum Hydroxide Adjuvant
L. Lin (2008)
Activation of dendritic cells and induction of CD4(+) T cell differentiation by aluminum-containing adjuvants.
A. Sokolovska (2007)
Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells
M. Kool (2008)
Aluminum Hydroxide Adjuvants Activate Caspase-1 and Induce IL-1β and IL-18 Release1
H. Li (2007)
Preformulation studies of Clostridium difficile toxoids A and B.
M. Salnikova (2008)
Effect of microenvironment pH of aluminum hydroxide adjuvant on the chemical stability of adsorbed antigen.
Arunee Wittayanukulluk (2004)
A rapid, three-step process for the preformulation of a recombinant ricin toxin A-chain vaccine.
Laura J. Peek (2007)
Mechanism of action of clinically approved adjuvants.
B. Lambrecht (2009)
The Nlrp3 inflammasome is critical for aluminium hydroxide‐mediated IL‐1β secretion but dispensable for adjuvant activity
L. Franchi (2008)
Effects of stabilizers on the destabilization of proteins upon adsorption to aluminum salt adjuvants.
Laura J. Peek (2007)
T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection
K. Korsholm (2010)
Relationship between physical and chemical properties of aluminum-containing adjuvants and immunopotentiation
S. Hem (2007)
Freezing temperatures in the vaccine cold chain: a systematic literature review.
D. Matthias (2007)
Mechanism of adsorption of hepatitis B surface antigen by aluminum hydroxide adjuvant.
Seema Iyer (2004)
How do adjuvants work? Important considerations for new generation adjuvants.
Amy S McKee (2007)
Towards an understanding of the adjuvant action of aluminium
P. Marrack (2009)
Characterization of a thermostable hepatitis B vaccine formulation.
L. Braun (2009)
Derivative absorbance spectroscopy and protein phase diagrams as tools for comprehensive protein characterization: a bGCSF case study.
L. Kueltzo (2003)
Degree of antigen adsorption in the vaccine or interstitial fluid and its effect on the antibody response in rabbits.
M. Chang (2001)
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
V. Hornung (2008)
Immunogenicity in mice of anthrax recombinant protective antigen in the presence of aluminum adjuvants.
I. Berthold (2005)
Relationship between the strength of antigen adsorption to an aluminum-containing adjuvant and the immune response.
Bethany Hansen (2007)
Inhibition of aggregation of aluminum hydroxide adjuvant during freezing and drying.
Amber L. Clausi (2008)
Relationship between the degree of antigen adsorption to aluminum hydroxide adjuvant in interstitial fluid and antibody production.
Seema Iyer (2003)
Dry powders of stable protein formulations from aqueous solutions prepared using supercritical CO(2)-assisted aerosolization.
S. Sellers (2001)
Effects of immobilization onto aluminum hydroxide particles on the thermally induced conformational behavior of three model proteins.
S. Bai (2009)
Influence of particle size and antigen binding on effectiveness of aluminum salt adjuvants in a model lysozyme vaccine.
Amber L. Clausi (2008)
Stabilizing formulations for inhalable powders of live-attenuated measles virus vaccine.
J. Burger (2008)
Novel cellular and molecular mechanisms of induction of immune responses by aluminum adjuvants.
V. Aimanianda (2009)
A heat-stable hepatitis B vaccine formulation
J. Jez̆ek (2009)
Effects of Adsorption to Aluminum Salt Adjuvants on the Structure and Stability of Model Protein Antigens*
L. Jones (2005)
Effect of the Degree of Phosphate Substitution in Aluminum Hydroxide Adjuvant on the Adsorption of Phosphorylated Proteins
Seema Iyer (2003)
Characterization of the freeze sensitivity of a hepatitis B vaccine
D. Chen (2009)
The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass.
U. Nygaard (2004)
Mechanism of freeze-thaw instability of aluminum hydroxycarbonate and magnesium hydroxide gels.
M. I. Zapata (1984)
Rate of Disappearance of Diphtheria Toxoid injected into Rabbits and Guinea-Pigs: Toxoid precipitated with Alum.
A. Glenny (1931)
A systematic approach to stabilizing EBA-175 RII-NG for use as a malaria vaccine.
Laura J. Peek (2006)
Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response.
Bethany Hansen (2009)
Immunology of TLR-independent vaccine adjuvants.
E. de Gregorio (2009)
Role of aluminum-containing adjuvants in antigen internalization by dendritic cells in vitro.
Garry L. Morefield (2005)
The structural stability of protein antigens adsorbed by aluminium hydroxide in comparison to the antigens in solutions
Yiwu Zheng (2007)
Evaluation of the compatibility of a second generation recombinant anthrax vaccine with aluminum-containing adjuvants.
S. Jendrek (2003)
Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants.
L. Braun (2009)
Structural changes of protein antigens due to adsorption onto and release from aluminium hydroxide using FTIR–ATR
Yiwu Zheng (2007)
Structural stability of hepatitis C virus envelope glycoprotein E1: effect of pH and dissociative detergents.
Feng He (2009)
Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants.
Ilia Z Romero Méndez (2007)
Evaluation of chemical degradation of a trivalent recombinant protein vaccine against botulinum neurotoxin by LysC peptide mapping and MALDI-TOF mass spectrometry.
Tia Estey (2009)
Relationship between tightness of binding and immunogenicity in an aluminum-containing adjuvant-adsorbed hepatitis B vaccine.
Patricia M Egan (2009)
Formation of Aqueous Small Droplet Aerosols Assisted by Supercritical Carbon Dioxide
R. Sievers (1999)
Stability of the Clostridium botulinum type A neurotoxin complex: an empirical phase diagram based approach.
D. Brandau (2007)
This paper is referenced by
Formulation and stabilization of recombinant protein based virus-like particle vaccines.
N. Jain (2015)
27Al and 31P NMR spectroscopy method development to quantify aluminum phosphate in adjuvanted vaccine formulations
Rahima Khatun (2018)
Synthetic adjuvants for vaccine formulations: phytol derivatives
S. K. Ghosh (2013)
Characterizing the Association Between Antigens and Adjuvants
Mette Hamborg (2015)
Particulate inorganic adjuvants: recent developments and future outlook
C. N. Maughan (2015)
Poly(lactic acid) and poly(lactic-co-glycolic acid) particles as versatile carrier platforms for vaccine delivery.
Vincent Pavot (2014)
"Reference values" of trace elements in the hair of a sample group of Spanish children (aged 6-9 years) - Are urban topsoils a source of contamination?
A. Pe (2014)
Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems
D. Krajišnik (2019)
Formulation Approaches and Strategies for Vaccines and Adjuvants
Kimberly J. Hassett (2013)
The impact of frost-damage on the quality and quantity of the secreted antigen-specific IgG repertoire.
Magda Rybczynska (2020)
Protein-excipient interactions: mechanisms and biophysical characterization applied to protein formulation development.
Tim J. Kamerzell (2011)
Stability of an aluminum salt-adjuvanted protein D-conjugated pneumococcal vaccine after exposure to subzero temperatures
Juliette Fortpied (2018)
Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components
R. D. Otto (2015)
Recent Advances on Fibrous Clay-Based Nanocomposites
E. Ruiz-Hitzky (2014)
Stabilization of tetanus toxoid formulation containing aluminium hydroxide adjuvant against freeze-thawing.
V. A. Solanki (2011)
Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts
C. Willhite (2014)
Characterization of TLR4 agonist effects on alhydrogel® sedimentation: a novel application of laser scattering optical profiling.
Christopher B Fox (2012)
Exercise-mediated changes in plasmacytoid dendritic cell production of IFNα and the effects of moderate intensity exercise on immune response to influenza infection and influenza vaccine
Justus E. Hallam (2013)
Beyond Empiricism: Informing Vaccine Development through Innate Immunity Research
S. Levitz (2012)
Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays
Jonathan C J Wei (2018)
Aluminum adjuvant dose guidelines in vaccine formulation for preclinical evaluations.
S. Vecchi (2012)
Hepatitis B monovalent vaccines produced by different manufacturers: comparative study on the quality of vaccine in period before and after the shelf life
Renata Faria de Carvalho (2015)
EVALUATION OF ALPHA-D-GLUCAN NANOPARTICLE AS A VACCINE ADJUVANT
Fangjia Lu (2016)
Identity, structure and compositional analysis of adjuvanted vaccines
Kristen Kalbfleisch (2018)
Allergen-specific immunotherapy in asthmatic children: from the basis to clinical applications
Z. Aryan (2013)
Biomonitoring of Aluminum in Urine of Young Lebanese Children Living in Beirut
Rania El-Majzoub (2020)
Emerging trends in eco-compliant, synergistic, and hybrid assembling of multifunctional polymeric bionanocomposites
Christopher Igwe Idumah (2016)
Identity, Structure and Compositional Analysis of Aluminum Phosphate Adsorbed Pediatric Quadrivalent and Pentavalent Vaccines
Kristen Kalbfleisch (2019)
Extracellular Matrix Adjuvant for Vaccines
Mark A. Suckow (2011)
Lipid‐Based Bio‐Nanohybrids for Functional Stabilisation of Influenza Vaccines
B. Wicklein (2012)
The adsorption of allergoids and 3-O-desacyl-4'-monophosphoryl lipid A (MPL®) to microcrystalline tyrosine (MCT) in formulations for use in allergy immunotherapy.
Andrew James Bell (2015)
Tracing Endotoxin Levels Throughout HPV16 L1 Vaccine Purification and Particle Production
M. Ryan (2017)See more