Molecular and functional characteristics of a protective human monoclonal antibody to serotype 8 Streptococcus pneumoniae capsular polysaccharide

Z. Zhong, T. Burns, Q. Chang, M. Carroll, Liise-anne Pirofski

Research output: Contribution to journalArticle

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Abstract

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(κ) [IgM(κ)] MAb D11 by Epstein-Bart virus transformation of peripheral lymphocytes from a Pneumovax recipient. Nucleic acid sequence analysis revealed that MAb D11 uses V3-15/V(H)3 and A20/(V)(κ) 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.

Original languageEnglish (US)
Pages (from-to)4119-4127
Number of pages9
JournalInfection and Immunity
Volume67
Issue number8
StatePublished - Aug 1999

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Streptococcus pneumoniae
Polysaccharides
Monoclonal Antibodies
Alternative Complement Pathway
Immunoglobulin M
Classical Complement Pathway
Pneumococcal Infections
Pneumococcal Vaccines
Lymphocyte Activation
Molecular Structure
Human Activities
Nucleic Acids
Capsules
Sequence Analysis
Serogroup
Viruses
Mutation
Survival
Antibodies
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Molecular and functional characteristics of a protective human monoclonal antibody to serotype 8 Streptococcus pneumoniae capsular polysaccharide. / Zhong, Z.; Burns, T.; Chang, Q.; Carroll, M.; Pirofski, Liise-anne.

In: Infection and Immunity, Vol. 67, No. 8, 08.1999, p. 4119-4127.

Research output: Contribution to journalArticle

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