title: Effect of the strength of adsorption of HIV 1 SF162dV2gp140 to aluminum-containing adjuvants on the immune response.
abstract: The importance of the strength of antigen adsorption by aluminum-containing adjuvants on immunopotentiation was studied using HIV 1 SF162dV2gp140 (gp140), a potential HIV/AIDS antigen. The strengths of adsorption by aluminum hydroxide (AH) adjuvant and aluminum phosphate adjuvant, as measured by the Langmuir adsorptive coefficient, were 1900 and 400 mL/mg, respectively. The strength of adsorption by AH was modified by pretreatment of AH with two different concentrations of potassium dihydrogen phosphate to produce phosphate-treated aluminum hydroxide adjuvants having adsorptive coefficients of 1200 and 800 mL/mg. The four adjuvants were used to prepare vaccines containing either 1 or 10 μg of gp140 per dose. Antibody studies in mice revealed that the presence of an adjuvant increased the immune response in comparison with a solution of gp140 when the dose was 1 μg. Furthermore, the immune response was inversely related to the adsorptive coefficient. In contrast, no significant difference in immunopotentiation was observed between treatments in the presence or absence of an adjuvant when the dose of gp140 was 10 μg. Analysis of the binding of gp140 to CD4 and anti-gp140 monoclonal antibodies by surface plasmon resonance suggests that tight binding induced structural changes in the antigen.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907-2091.
authors.forename: Bethany
authors.initials: B
authors.lastname: Hansen
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139; MedImmune, Mountain View, California 94043.
authors.forename: Padma
authors.initials: P
authors.lastname: Malyala
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139.
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139.
authors.forename: Yide
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139; Vaccine Research Center, NIAID, NIH, Gaithersburg, Maryland 20878.
authors.forename: Indresh
authors.initials: I
authors.lastname: Srivastava
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana 47907. Electronic address: hogenesch@purdue.edu.
authors.forename: Harm
authors.initials: H
authors.lastname: Hogenesch
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907-2091.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hem
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000327:Adsorption; D000536:Aluminum Hydroxide / Q000737:chemistry*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D004339:Drug Compounding; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D020349:Surface Plasmon Resonance; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D000536:Aluminum Hydroxide