COMPARISON OF ADJUVANT ACTIVITIES OF ALUMINUM PHOSPHATE, CALCIUM-PHOSPHATE AND STEARYL TYROSINE FOR TETANUS TOROID

被引:61
作者
GUPTA, RK
SIBER, GR
机构
[1] Massachusetts Public Health Biologic Laboratories, State Laboratory Institute, Jamaica Plain
关键词
D O I
10.1006/biol.1994.1008
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The adjuvant activity of three adjuvants, aluminium phosphate (AlPO4), calcium phosphate (CaHPO4) and stearyl tyrosine for tetanus toxoid (TT) were compared to soluble TT in mice at a dose of 0.5 Lf (1/10th of the single human dose) and in guinea-pigs at a dose of 7.5 Lf (1.5 times the single human dose). Three TT preparations varying in purity were used: (1) ammonium sulphate precipitated formalin detoxified tetanus toxin (AS-TT); (2) AS-TT ultrafiltered to remove low molecular weight peptides (UF-TT); and (3) chromatographically purified tetanus toxin subsequently detoxified with formalin (CP-TT). After primary immunization of mice, AlPO4adsorbed TTs induced higher toxin-neutralizing and IgG (by ELISA) antibodies than CaHPO4, stearyl tyrosine adsorbed or soluble TT preparations, but this difference was no longer present after secondary immunization. TT preparations of varying purities showed similar antibody responses after primary and secondary immunizations when adsorbed on each adjuvant. CP-TT preparation showed the highest neutralizing antibody level amongst soluble preparations after the first dose. All the preparations induced mainly IgG1 antibodies. However, stearyl tyrosine adsorbed TT induced relatively higher IgG2a and IgG2b responses than AlPO4, CaHPO4adsorbed or soluble TTs particularly after booster injection. No preparation induced detectable IgG3 or IgM antibodies. AlPO4adsorbed preparations induced higher IgE antibodies than CaHPO4and stearyl tyrosine adsorbed vaccines. Among the soluble preparations, CP-TT induced lower anti-TT IgE antibodies than standard AS-TT. All these preparations were also tested in the US potency test for adsorbed TT in guinea-pigs. While all the preparations passed this test, AlPO4adsorbed TT preparations induced higher neutralizing and IgG antibodies than CaHPO4and stearyl tyrosine adsorbed or soluble TT preparations. In these animal models, purified TT was a strong immunogen and traditional AlPO4adjuvant gave the highest antibody responses. © 1994 by Academic Press, Inc.
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页码:53 / 63
页数:11
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