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Infection and Immunity, August 1999, p. 4119-4127, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Molecular and Functional Characteristics of a Protective Human Monoclonal Antibody to Serotype 8 Streptococcus pneumoniae Capsular Polysaccharide

Z. Zhong,1 T. Burns,2 Q. Chang,2 M. Carroll,3 and L. Pirofski1,2,*

Department of Medicine, Division of Infectious Diseases,1 and Department of Microbiology and Immunology,2 Albert Einstein College of Medicine, Bronx, New York, and The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts3

Received 26 March 1999/Returned for modification 4 May 1999/Accepted 15 May 1999

The structural characteristics and biological activity of human antibodies that are reactive with the capsular polysaccharides of most serotypes of Streptococcus pneumoniae, including serotype 8, are unknown. This paper describes the generation, molecular structure, and protective efficacy of a human monoclonal antibody (MAb) reactive with the capsular polysaccharide of serotype 8 Streptococcus pneumoniae. We generated the immunoglobulin M(kappa ) [IgM(kappa )] MAb D11 by Epstein-Barr virus transformation of peripheral lymphocytes from a Pneumovax recipient. Nucleic acid sequence analysis revealed that MAb D11 uses V3-15/VH3 and A20/Vkappa gene segments with evidence of somatic mutation. In vitro studies revealed MAb D11-dependent complement deposition on the capsule of serotype 8 organisms via either the classical or the alternative complement pathway. In vivo, MAb D11 prolonged the survival of both normal and C4-deficient mice with lethal serotype 8 S. pneumoniae infection. Our findings demonstrate that a serotype-specific human IgM with certain structural and functional characteristics was protective in mice lacking a functional classical complement pathway and show that alternative complement pathway activation is an important determinant of pneumococcal protection.

* Corresponding author. Mailing address: Division of Infectious Diseases, Albert Einstein College of Medicine, Room 402 Forchheimer, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-2372. Fax: (718) 430-8968. E-mail: pirofski{at}aecom.yu.edu.

Infection and Immunity, August 1999, p. 4119-4127, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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