作为无细胞百日咳疫苗和全细胞百日咳疫苗反应测量方法的功能测定与酶免疫测定之间的关系。

Relationships between functional assays and enzyme immunoassays as measurements of responses to acellular and whole-cell pertussis vaccines.

作者信息

Meade B D, Lynn F, Reed G F, Mink C M, Romani T A, Deforest A, Deloria M A

机构信息

Division of Bacterial Products, Food and Drug Administration, Rockville, MD 20852-1448, USA.

出版信息

Pediatrics. 1995 Sep;96(3 Pt 2):595-600.

PMID:7659484

Abstract

OBJECTIVE

To examine the relationships between functional assays and antigen-specific enzyme immunoassays in sera from a multicenter trial of 13 different experimental acellular pertussis vaccines and 2 licensed whole-cell vaccines, and to determine whether correlations previously observed among assays of specimens from pertussis patients and whole-cell vaccinees would apply to specimens from infants immunized with purified components in acellular vaccines.

METHODS

Postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin (PT), filamentous hemagglutinin, pertactin (PRN), and a mixture of types 2 and 3 fimbriae (FIM) by enzyme-linked immunosorbent assay, for whole-cell agglutinins (AGGs) and for PT-neutralizing antibodies by the Chinese hamster ovary (CHO) cell assay. Assay results were compared for individual sera, as well as for geometric mean antibody concentrations or titers (GMTs) calculated by vaccine or overall.

RESULTS

For the 15 vaccines, the PT GMTs were highly correlated with the CHO assay GMTs (r = .92), and the FIM GMTs were highly correlated with the AGG GMTs (r = .96). For individual postvaccination sera, there was a significant correlation between the CHO titers and levels of antibody to PT whether the 15 vaccines were considered separately (.59 < or = r < or = .85) or combined (r = .81). For individual sera from infants immunized with the two whole-cell vaccines or any of the four acellular vaccines containing FIM, a strong correlation between AGG titer and FIM antibody was observed whether the vaccines were considered separately (.83 < or = r < or = .91) or together (r = .86). One vaccine without detectable FIM produced a measurable AGG response; for this vaccine, a moderate but significant correlation (R = .58) between PRN antibody and AGG titer was observed.

CONCLUSION

These data indicate that appropriate antigen-specific enzyme-linked immunosorbent assays will furnish results similar to those provided by the CHO and AGG assays in the evaluation of the immunogenicity of component vaccines. Antibodies to FIM seem to include the most important AGGs; however, there is evidence that agglutination by PRN antibody may be detected in the absence of antibody to FIM.

摘要

目的

在一项针对13种不同实验性无细胞百日咳疫苗和2种已获许可的全细胞疫苗的多中心试验中，研究血清中功能测定与抗原特异性酶免疫测定之间的关系，并确定先前在百日咳患者和全细胞疫苗接种者标本检测中观察到的相关性是否适用于接种无细胞疫苗中纯化成分的婴儿标本。

方法

采用酶联免疫吸附测定法检测免疫后血清中针对百日咳毒素（PT）、丝状血凝素、百日咳黏附素（PRN）以及2型和3型菌毛混合物（FIM）的免疫球蛋白G抗体，采用中国仓鼠卵巢（CHO）细胞测定法检测全细胞凝集素（AGGs）和PT中和抗体。对个体血清以及按疫苗或总体计算的几何平均抗体浓度或滴度（GMTs）的检测结果进行比较。

结果

对于这15种疫苗，PT GMTs与CHO测定的GMTs高度相关（r = 0.92），FIM GMTs与AGG GMTs高度相关（r = 0.96）。对于个体接种疫苗后的血清，无论单独考虑这15种疫苗（0.59≤r≤0.85）还是综合考虑（r = 0.81），CHO滴度与PT抗体水平之间均存在显著相关性。对于接种两种全细胞疫苗或任何一种含FIM的四种无细胞疫苗的婴儿的个体血清，无论单独考虑这些疫苗（0.83≤r≤0.91）还是一起考虑（r = 0.86），均观察到AGG滴度与FIM抗体之间有很强的相关性。一种未检测到FIM的疫苗产生了可测量的AGG反应；对于这种疫苗，观察到PRN抗体与AGG滴度之间存在中等但显著的相关性（R = 0.58）。