Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response

Abstract Hepatitis B surface antigen (HBsAg) is known to adsorb to aluminum hydroxide adjuvant (AH) by ligand exchange between its accessible phosphate groups and surface hydroxyl groups of the adjuvant. To study the effect of the binding strength, five vaccines were prepared with AH or four samples...

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Bibliographic Details
Published in:Vaccine 2009-02, Vol.27 (6), p.888-892
Main Authors: Hansen, Bethany, Belfast, Mary, Soung, George, Song, Liping, Egan, Patricia M, Capen, Robert, HogenEsch, Harm, Mancinelli, Ralph, Hem, Stanley L
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - metabolism
Adjuvants, Immunologic - pharmacology
Adsorption
Adsorptive coefficient
Allergy and Immunology
Aluminum
Aluminum Hydroxide - metabolism
Aluminum Hydroxide - pharmacology
Aluminum hydroxide adjuvant
Animals
Antigen adsorption
Applied microbiology
Biological and medical sciences
Degree of elution
Female
Fundamental and applied biological sciences. Psychology
Hemodialysis
Hepatitis
Hepatitis B Antibodies - blood
Hepatitis B surface antigen
Hepatitis B Surface Antigens - immunology
Hepatitis B Surface Antigens - metabolism
Hepatitis B Vaccines - immunology
Immune response
Immunogenicity
Laboratory animals
Ligand exchange
Ligands
Medical research
Mice
Microbiology
Miscellaneous
Molecular weight
Proteins
Studies
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Virology
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Summary:Abstract Hepatitis B surface antigen (HBsAg) is known to adsorb to aluminum hydroxide adjuvant (AH) by ligand exchange between its accessible phosphate groups and surface hydroxyl groups of the adjuvant. To study the effect of the binding strength, five vaccines were prepared with AH or four samples of AH that were modified by pretreatment with different concentrations of potassium dihydrogen phosphate. The adsorptive coefficients ranged from 3660 to 250 mL/mg based on the Langmuir adsorption isotherm and degrees of elution ranged from 1 to 31% when the vaccines were exposed to interstitial fluid in vitro. When tested in mice the four vaccines containing phosphate-treated AH (PTAH) induced significantly greater antibody responses than the vaccine containing AH, which had the highest adsorptive coefficient and the smallest degree of elution of HBsAg. The results indicated that antibody production is reduced when the antigen is adsorbed too strongly. Thus, the strength of adsorption of the antigen to an aluminum-containing adjuvant can affect the immunogenicity of the vaccine and should be optimized during vaccine formulation.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2008.11.078