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Infection and Immunity, May 1999, p. 2366-2370, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Avidity as a Determinant of the Protective Efficacy of Human Antibodies to Pneumococcal Capsular Polysaccharides

William R. Usinger, and Alexander H. Lucas*

Children's Hospital Oakland Research Institute, Oakland, California 94609

Received 25 November 1998/Returned for modification 13 January 1999/Accepted 11 February 1999

Antibodies reactive with capsular polysaccharides are considered the principal mediators of immunity against invasive diseases caused by Streptococcus pneumoniae. In this study, we tested the hypothesis that anti-pneumococcal capsular polysaccharide (PPS) antibody avidity can influence protective efficacy. We measured the avidities of individual adult postvaccination immunoglobulin G2 (IgG2) antibodies to PPS serotypes 6B and 23F and examined the relationship between avidity and opsonophagocytic and mouse-protective activities. The avidities of PPS 6B- and PPS 23F-specific IgG2 antibodies ranged from 6 to 31 nM-1 and from 3 to 20 nM-1, respectively. We observed an inverse correlation between the magnitude of avidity and the amount of antibody required to protect mice against lethal bacteremia caused by serotype 6B pneumococci. Similarly, higher-avidity antibodies were more effective than lower-avidity antibodies in vitro in mediating complement-dependent opsonophagocytosis of both 6B and 23F pneumococci. These data suggest that in adults, PPS antibodies are sufficiently polymorphic to possess biologically significant variations in avidity. We conclude that avidity functions as an important determinant of anticapsular antibody protective efficacy against pneumococci.

* Corresponding author. Mailing address: Children's Hospital Oakland Research Institute, 747 52nd St., Oakland, CA 94609. Phone: (510) 428-3175. Fax: (510) 428-3608. E-mail: alucas{at}mail.cho.org.

Infection and Immunity, May 1999, p. 2366-2370, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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