Designing new vaccines

19-11-2009

BioXtal and NovartisVaccines used the MXpress service to determine the structure of a Meningitis B cell-surface protein in complex with a neutralising antibody.

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The challenge
Current meningitis vaccines are not efficient against Meningitis B strains as they target the surface carbohydrates of meningitis bacteria which, in B strains, are identical to human motifs.

Background
In order to find new and efficient vaccine targets, NovartisVaccines tested the immunogenicity and protective activity in vivo of a large number of cell surface-exposed proteins from Meningococcus B. Amongst these only a limited number of proteins was able to induce protective antibodies. One protein, NMB033, induces protective immunity in mice. Immunological studies demonstrated that this is due to the ability of the protein to efficiently mimic an unrelated epitope of a well-known antigen named porA. Structural information is a fundamental element in elucidating such molecular mimicry, as well as in understanding the mechanisms through which some antibodies elicit microbicidal response.

Results
Data collected using the MXpress service have led to the elucidation of the structural basis for the recognition of the NMB0033 protein by a Meningitis B neutralising antibody.

How did the synchrotron help?
Poor quality crystals of this protein complex did not show diffraction on a conventional X-ray source and thus required a powerful synchrotron beamline for data collection. The high intensity and variable beam size of beamline ID14-4 helped to find the best diffracting part of the crystal and to obtain the best data.

The future
Better vaccines through a better understanding of bactericidal responses that start with an antigen-antibody recognition event.

 

Top image: The crystal structure of the antibody chains (pink and blue) bound to the meningitis antigen NMB003 (green). Image courtesy of L. Vuillard, BioXtal.