Optimization and Validation of a Multiplex, Electrochemiluminescence-Based Detection Assay for the Quantitation of Immunoglobulin G Serotype-Specific Antipneumococcal Antibodies in Human Serum

American Society for Microbiology - Tập 16 Số 3 - Trang 387-396 - 2009
Rocio D. Marchese1,2,3, Derek Puchalski1,2,4, Pamela Miller1,2, Joseph Antonello1,2, Olivia Hammond1,2,4, Tina Green1,2, Leonard J. Rubinstein1,2,4, Michael J. Caulfield1,2,4, Daniel J. Sikkema1,2,4
1ID/Vaccines, Merck Research Laboratories, Upper Gwynedd, Pennsylvania
2Non-Clinical Statistics, Merck Research Laboratories, West Point, Pennsylvania
3Wayne Clinical Support, Merck Research Laboratories, Wayne, Pennsylvania, USA.
4Wayne Clinical Support, Merck Research Laboratories, Wayne, Pennsylvania

Tóm tắt

ABSTRACT Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides (Ps) from 23 of the most prevalent serotypes of Streptococcus pneumoniae . Testing of vaccine immunogenicity has been historically performed on the enzyme-linked immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG) antibodies to all 23 serotypes included in Pneumovax 23. In order to significantly improve the throughput of this form of testing, we have developed and validated a direct binding electrochemiluminescence (ECL)-based multiplex assay that can measure the antibody response in human serum to eight serotypes within a single microtiter well. The pneumococcal (Pn) ECL assay is based on the Meso Scale Discovery (MSD) technology which utilizes a Sulfo-Tag-labeled anti-human IgG antibody that emits light upon electrochemical stimulation. The Pn ECL assay exhibits a wide dynamic range and provides the ability to read concentrations down to the minimum reported concentration in the Merck ELISA (0.1 μg/ml). Cross-reactivity assessment using type-specific monoclonal antibodies showed no cross talk between antigen spots within a well. By use of the WHO Pn sample reference panel, the results obtained with the Pn ECL assay were compared to the results obtained with the international Pn ELISA. The results for the Pn ECL assay satisfied the WHO-recommended acceptance criterion for concordance for all seven serotypes with published Pn ELISA values, and the overall correlation ( r value) across the seven serotypes was 0.994. The MSD methodology has great potential to be extremely useful for simultaneously quantitating IgG responses to several Pn serotypes while conserving serum volumes and laboratory testing time.

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American Society for Microbiology

Tập 16 Số 3

387-396

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