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, L. Pirofski, T. R. Kozel
1999 Infection and Immunity  
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 8Streptococcus pneumoniae. We generated the immunoglobulin M(κ) [IgM(κ)] MAb D11 by Epstein-Barr virus transformation
more » ... irus transformation of peripheral lymphocytes from a Pneumovax recipient. Nucleic acid sequence analysis revealed that MAb D11 uses V3-15/VH3 and A20/Vκ 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 8S. 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.
doi:10.1128/iai.67.8.4119-4127.1999 fatcat:nksjkpviobhnhhwnxhvfk4lbla