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Clinical and Vaccine Immunology, April 2007, p. 397-403, Vol. 14, No. 4
1071-412X/07/$08.00+0     doi:10.1128/CVI.00241-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Avidity of the Immunoglobulin G Response to a Neisseria meningitidis Group C Polysaccharide Conjugate Vaccine as Measured by Inhibition and Chaotropic Enzyme-Linked Immunosorbent Assays

Shannon L. Harris,¹ How Tsao,¹ Lindsey Ashton,² David Goldblatt,² and Philip Fernsten^1*

Wyeth Vaccines Research, Pearl River, New York,¹ Immunobiology Unit, Institute of Child Health, London, United Kingdom²

Received 30 June 2006/ Returned for modification 28 July 2006/ Accepted 31 January 2007

Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (K_Ds) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol. After the primary immunization series, the geometric mean (GM) K_D was 674 nM and did not change in the months following immunization. However, the GM avidity did increase after the booster dose (GM K_D, 414 nM 1 month after booster immunization). In contrast, the GM AI increased from an initial value of 118 after the primary immunization series to 147 6 months after the completion of the primary immunization series and then further increased to 178 after booster immunization. At the individual subject level, the avidity constant and AI correlated after the primary immunization series and after booster immunization but not prior to boosting. This work suggests that the AI, as measured by the chaotropic ELISA, in contrast to the K_D, reflects changes that render antibody populations less susceptible to disruption by chaotropic agents without directly affecting the strength of the binding interactions.

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* Corresponding author. Mailing address: Wyeth Vaccines Research, 401 N. Middletown Road, Pearl River, NY 10965. Phone: (845) 602-3602. Fax: (845) 602-4126. E-mail: Fernstp{at}Wyeth.com

Published ahead of print on 7 February 2007.

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Clinical and Vaccine Immunology, April 2007, p. 397-403, Vol. 14, No. 4
1071-412X/07/$08.00+0     doi:10.1128/CVI.00241-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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