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Clinical and Vaccine Immunology, January 2009, p. 37-42, Vol. 16, No. 1
1071-412X/09/$08.00+0     doi:10.1128/CVI.00290-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Thermodynamics and Density of Binding of a Panel of Antibodies to High-Molecular-Weight Capsular Polysaccharides{triangledown}

Shannon L. Harris and Philip Fernsten*

Wyeth Vaccines Research, Pearl River, New York

Received 11 August 2008/ Returned for modification 12 September 2008/ Accepted 3 November 2008

The interaction between antipolysaccharide (anti-PS) antibodies and their antigens was investigated by the use of isothermal titration calorimetry to determine the thermodynamic binding constant (K), the change in the enthalpy of binding ({Delta}H), and the binding density (N) to high-molecular-weight PSs. From these values, the change in the entropy of binding ({Delta}S) was calculated. The thermodynamic parameters of binding to high-molecular-weight capsular PSs are reported for two monoclonal antibodies (MAbs) with different specificities for meningococcal serogroup C PS, five MAbs specific for different pneumococcal serotypes, and the Fab fragments of two antipneumococcal MAbs. The K values were in the range of 106 to 107 M–1, and these values were 1 to 2 orders of magnitude greater than the previously reported K values derived from antibody-oligosaccharide interactions. The {Delta}H associated with binding was favorable for each MAb and Fab fragment. The {Delta}S associated with binding was also generally favorable for both the MAbs and the Fab fragments, with the exception of the anti-serotype 14 MAb and its Fab fragment. N provides information regarding how densely MAbs or Fabs can bind along PS chains and, as expressed in terms of monosaccharides, was very similar for the seven MAbs, with an average of 12 monosaccharides per bound MAb. The value of N for each Fab was smaller, with five or seven monosaccharides per bound Fab. These results suggest that steric interactions between antibody molecules are a major influence on the values of N of high-affinity MAbs to capsular PSs.

* Corresponding author. Mailing address: Wyeth Vaccines Research, 401 N. Middletown Road, Pearl River, NY 10965. Phone: (845) 602-3602. Fax: (845) 602-5296. E-mail: Fernstp{at}Wyeth.com

{triangledown} Published ahead of print on 12 November 2008.

Clinical and Vaccine Immunology, January 2009, p. 37-42, Vol. 16, No. 1
1071-412X/09/$08.00+0     doi:10.1128/CVI.00290-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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