Background: Streptococcus pneumoniae remains an important cause of morbidity and mortality in both adults and children world-wide. The increasing isolation of pneumococci resistant to penicillin and other antimicrobial agents has increased the urgency with which safe and effective methods of preventing pneumococcal infection are pursued. The poor immunogenicity of carbohydrates in those most at risk of invasive pneumococcal infections has hampered the development of an effective pneumococcal vaccine. However, the recent success of the Haemophilus influenzae type b (Hib)-protein conjugate vaccines in eradicating invasive Hib infection in children under five years of age has highlighted the success of bacterial conjugate vaccine technology. Pneumococcal polysaccharide-protein conjugate vaccines, are currently being developed by a number of vaccine manufacturers and several have entered Phase II and one, phase III studies in Europe.
Problems however, surround the measurement and interpretation of pneumococcal type specific antibody titres which are used as surrogate markers of protection when evaluating the immunogenicity of pneumococcal vaccines, and large inter-laboratory variations exist. Furthermore, there is little agreement on in-vitro correlates of immunological protection for the pneumococcus and no large scale comparative studies have been performed.
Objectives: This concerted action seeks to bring together laboratories currently actively engaged in pneumococcal research to: 1) optimise and quality control anti-pneumococcal type specific antibody assays across Europe and 2) compare and standardise in- vitro correlates and animal models of protection. Proposal Content: Workpackage 1 will involve the distribution of a new European secondary pneumococcal standard serum and 20 pairs of pre and post-vaccination quality control sera, in two stages, to all participants.
Antibody titres in the QC sera will be determined by the participating laboratories using standardised methodology.
During the 2 stages of the workprogramme assays will be refined and optimised so that there is good agreement between European laboratories measuring anti- pneumococcal antibodies. Workpackage 2 will utilise the same sera in a variety of different assays which seek to determine in-vitro correlates of protection. Assays determining antibody isotype, antibody avidity, opsonophagocytic activity and bactericidal activity are all currently established in participating laboratories. These assays will be compared between laboratories and the performance of individual sera in animal protection assays will be correlated with the various in-vitro parameters mentioned above. Such comparisons will permit the identification of assays that correlate well with protection, do not require the use of animals and can be applied on a large scale to vaccine studies.
Benefits: Such an initiative would be highly relevant to future pneumococcal vaccine studies in Europe as the use of a comparable antibody assay would permit comparison of immunogenicity data obtained from studies in different member states. This would prevent the costly duplication of vaccine studies in individual member states and hasten uniform vaccine licensing procedures. Furthermore this concerted action would serve as a model for the evaluation of new bacterial conjugate vaccines and correlates of protection defined in this concerted action could be rapidly evaluated for a number of other potential vaccines including those designed to prevent Group B Streptococcus, Staphylococcus aureus, Shigella dysenteriae, Klebsiella pneumoniae, Escherichia coli, Salmonella typhi and N. meningitidis. Comparing and evaluating in-vitro correlate of protection assays would greatly enhance the relevance and applicability of such models to large vaccine studies and would permit important vaccine evaluation to take place prior to costly phase II and III studies. In addition, such an initiative would reduce the need for animal experimentation by providing alternative methods of evaluation.