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© The Rockefeller University Press, 0022-1007/1997/6/1929/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 11, June 2, 1997 1929-1938

Article

N-Propionylated Group B Meningococcal Polysaccharide Mimics a Unique Bactericidal Capsular Epitope in Group B Neisseria meningitidis

Robert A. Pon, Michele Lussier, Qing-Ling Yang, and Harold J. Jennings

From the Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6

The N-propionylated group B meningococcal polysaccharide (NPrGBMP) mimics a unique protective epitope on the surface of group B meningococci (GBM) and Escherichia coli K1. Using a series of monoclonal antibodies (mAbs) induced by the NPrGBMP–monomeric tetanus toxoid (TT) conjugate vaccine it was demonstrated that mAbs having specificities for both extended and conventional short segments of the NPrGBMP were formed, but only the former were bactericidal, and/or gave passive protection against live challenge by GBM. The failure of mAbs specific for short epitopes to protect was further established when (NeuPr)4–TT was used as the vaccine. Of all the mAbs produced that were specific for short internal segments of the NPrGBMP, none were protective, despite the fact that most of them cross-react with the GBM capsular polysaccharide. In contrast, most of the protective mAbs produced by NPrGBMP– TT did not recognize the group B meningococcal polysaccharide (GBMP) unless it was present in its aggregated high molecular weight form. The bactericidal epitope mimicked by the NPrGBMP was shown to be ubiquitous in the capsule of both GBM and E. coli K1 using immunogold labeling techniques and, because of its unique properties, its identification could be significant in the development of a comprehensive conjugate vaccine against group B meningococcal meningitis. This is because most known human {alpha}(2–8)-polysialic acid self-antigens can be accommodated in 30–50 {alpha}(2–8)-linked sialic acid residues, which is roughly equivalent to an 11-kD length of the GBMP. It has been hypothesized that the formation of the protective epitope on the surface of GBM is due to the interaction of helical segments of the GBMP with another molecule and that the protective epitope is mimicked by the NPrGBMP. Support for the above hypothesis is provided by the fact that the protective NPrGBMP epitope has a similar unusual length dependency to that of the GBMP epitope.

Address correspondence to Dr. Harold J. Jennings, Institue for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6.

This is National Research Council of Canada publication Number 39555 and the work was supported in part by North American Vaccines, Beltsville, MD.

1Abbreviations used in this paper: GBM, group B meningococci; GBMP, group B meningococcal polysaccharide (11 kD); hmw, high molecular weight; HSA, human serum albumin; N-CAM, neural cell adhesion; NeuPr, N-propionylated sialic acid; NMR, nuclear magnetic resonance spectroscopy; NPrGBMP, N-propionylated GBMP (11 kD); TT, monomeric tetanus toxoid.


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