Effect of the Strength of Adsorption of HIV 1 SF162dV2gp140 to Aluminum-Containing Adjuvants on the Immune Response

被引:20
|
作者
Hansen, Bethany [2 ]
Malyala, Padma [3 ]
Singh, Manmohan [3 ]
Sun, Yide [3 ]
Srivastava, Indresh [3 ]
Hogenesch, Harm [1 ]
Hem, Stanley L. [2 ]
机构
[1] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA
[2] Purdue Univ, Dept Ind & Phys Pharm, W Lafayette, IN 47907 USA
[3] Novartis Vaccines & Diagnost, Cambridge, MA 02139 USA
关键词
excipients; protein formulation; proteins; vaccines; vaccine adjuvants; HUMAN-IMMUNODEFICIENCY-VIRUS; HYDROXIDE ADJUVANT; ANTIGEN ADSORPTION; PARTIAL DELETION; PHOSPHATE; IMMUNOGENICITY; ANTIBODIES; VACCINES; BINDING;
D O I
10.1002/jps.22555
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 : g 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 : g. 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 : g. 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. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 3245-3250, 2011
引用
收藏
页码:3245 / 3250
页数:6
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