Streptococcus Pneumoniae, the pneumococcus, is one of the leading causes of pneumonia, sepsis and meningitis worldwide
Disease rates in vaccine-specific serotypes have dropped rapidly in infants since polysaccharide vaccines – and later pneumococcal conjugate vaccines – were introduced. But disease rates in non-vaccine types have increased, driving the development of higher valency vaccines to cover a wider range of serotypes.
The group is associated with many of the current vaccine developments and advises vaccine companies and bodies such as the European Medicines Agency (EMA) and the European Directorate for the Quality of Medicines (EDQM). NIBSC has also contributed to World Health Organisation (WHO) technical reports on pneumococcal vaccine development and assay standardisation.
Members of our group have a wide set of skills and we actively collaborate with vaccine manufactures and developers, academic research and government and non-government agencies.
As a member of the Official Medicines Control Laboratories (OMCL) network, NIBSC currently fulfils the Official Control and Batch Release (OCABR) of pneumococcal polysaccharide vaccines. We also test many other polysaccharide conjugate vaccines with similar release tests. For the upstream drug substances and final drug product, testing confirms:
Because of the highly complex nature of multivalent pneumococcal vaccines, the OMCL network allows certification of individual serotype specific bulk conjugates before the final product is released. This means the OCABR workload for testing can be spread to several OMCLs.
NIBSC stocks several standards and quality control serum samples to use with the WHO ELISA to quantify serotype specific antibodies. In 2007 NIBSC was part of the group which published the creation of the serum standard 007SP as a replacement for 89-SF. Subsequently 007SP was established as the 1st international standard in 2010. This standard is available in the NIBSC catalogue. 007SP WHO International Standard or Reference Reagent
NIBSC supplies the ELISA Quality Control panel – 12 serum samples for which the antibody concentration for 13 serotypes has been established. This panel allows laboratories to assess the accuracy of newly established ELISA assays. Stock levels are carefully controlled and requests need to be authorised before ordering. For authorisation contact Prof David Goldblatt at The Institute of Child Health London with a short description of your intended use for the panel. NIBSC also has large stocks of pooled serum from pre- and post-vaccinees. For information, contact us.
The OPA quantifies functional antibodies and is currently used for evaluating vaccine efficacy. NIBSC is part of a consortium of laboratories – from industry, government and academia – aiming to improve OPA standardisation. For more details on OPA and ELISA see the Bacterial Respiratory Pathogen Reference Laboratory at the University of Alabama at Birmingham
NIBSC does not currently stock any typing antibodies, standards or reference materials but we welcome any suggestions on future development in this area.
Our group has led and collaborated in several research projects over the years. NIBSC’s unique function means we focus on research into developing innovative assays used to ensure safety and efficacy of vaccines and physical chemistry of the capsule polysaccharide. We collaborate with academic and commercial laboratories, helping decipher the intricacies of vaccines’ content, immunogenicity and safety.
Pneumococci are enclosed within a capsule consisting of repeated units of oligosaccharides, the composition of which defines the capsular type. As a result of vaccine pressure a number of strains express capsular polysaccharides with slight alterations which can lead to discrepancies between typing methods. Genetic differences of the capsule loci can be often be detected, but is difficult to link to capsule structure, while typing antibodies can cross-react between closely related capsules. Our group has been working with the collaborators at St George’s University, London to purify capsular polysaccharide from strains which have conflicting typing results. Structural analysis is carried out using binuclear magnetic resonance (NMR), and comparison to our polysaccharide database can give definitive characterisation of the capsule.
The ever-increasing valency of the pneumococcal conjugate vaccines means increasingly complex assays for vaccine evaluation are needed. We developed a competitive multiplex immuno assay for the quantification of serotype specific polysaccharide in pneumococcal vaccines.
In collaboration with the cellular imaging group, we have studied characterisation of cell lines and differentiation methods for the production of phagocytic cell for use in the opsonophagocytic assay.
Dr Rory Care - Principal Scientist
007sp: Human Anti-Pneumococcal capsule Reference Serum