Locating the structural and immunological basis for protection of a new MenB recombinant vaccine.
Angela Martino, Dr Barbara Bolgiano, Prof Ian Feavers
- Start Date:
01 January 2006
National Institute for Biological Standards and Control, Hertfordshire, UK
A study of the structural and in vivo and in vitro pre-clinical immunology of a recombinant outer membrane protein vaccine developed at Chiron Vaccines is to be carried out at the National Institute for Biological Standards and Control. The vaccine includes E. coli-produced polypeptides including a fusion of two antigens, all known to be surface expressed, play integral roles in cell structure or function, and produce bactericidal antibodies. An evaluation of the antigens' quality will be carried out with structural methods established in the primary applicant's laboratory. Single particle analysis of the antigens and accessibility of epitopes in the final combination will be determined by electron microscopy in the Cell Biology & Imaging Division. Functional antibody (Ab) production to individual antigens and a combination will be assessed by serum bactericidal assay titres in a mouse model using a panel of U.K. -relevant, homologous and reference strains. In vitro human immune cells will be used to measure cytokine responses. The ability of immune sera to recognize the vaccine-specific antigens on the surface of a panel of N. meningitis strains will be carried out using microscopy. Results from this study will be compared with those obtained from clinical trials with an identical vaccine combination. A critical assessment of the structural and epitope stability and accessibility in the recombinant vaccine will lead to a better understanding of the molecular markers necessary for quality assurance, and ultimately to the success of this group B meningococcal recombinant candidate as a immunogenic and cross-protective vaccine.