Title: Developing a multivalent Streptococcus pneumoniae recombinant glycoconjugate vaccine for preventing meningitis
Funder: Meningitis Now

Abstract: The bacterium pneumococcus is a common cause of meningitis. The pneumococcus is surrounded by a capsule layer made of sugars, which varies in structure between different strains. Vaccines targeting the capsule prevent pneumococcal meningitis but are expensive and at present only prevent infection with 13 of the 95+ different capsule types. Hence cheaper effective vaccines that prevent infection by all types of pneumococcus are needed, ideally based on proteins that are present in all pneumococci. We have developed a new technique that uses bacterial enzymes to combine capsule and protein vaccines, Protein Glycan Coupling Technology (PGCT), which could be cheaper and more flexible than existing methods. Using PGCT we can have combined one capsule vaccine (serotype 4) with three different protein vaccines and shown that when used as a vaccine this protects mice against pneumococcal meningitis. For this work we will widen the scope of the previous work to investigate whether the vaccine can be effective against multiple different capsular serotypes rather than just the one, and to include the most important capsular serotype for meningitis prevention (serotype 1). In addition we will test pneumococcal proteins that are found in higher quantities during meningitis to see whether they are effective vaccine candidates that can help prevent meningitis. The results of the work provide us with the necessary data on this vaccine approach for it to be developed and used in early phase clinical trials to demonstrate the vaccine is at least as good as the existing one.

Lay abstract: The bacterium pneumococcus is a common cause of meningitis. The pneumococcus is surrounded by a capsule layer made of sugars, which varies in structure between different strains. Vaccines targeting the capsule prevent pneumococcal meningitis but are expensive and at present only prevent infection with 13 of the 95+ different capsule types. Hence cheaper effective vaccines that prevent infection by all types of pneumococcus are needed, ideally based on proteins that are present in all pneumococci. We have developed a new technique that uses bacterial enzymes to combine capsule and protein vaccines, Protein Glycan Coupling Technology (PGCT), which could be cheaper and more flexible than existing methods. Using PGCT we can have combined one capsule vaccine (serotype 4) with three different protein vaccines and shown that when used as a vaccine this protects mice against pneumococcal meningitis. For this work we will widen the scope of the previous work to investigate whether the vaccine can be effective against multiple different capsular serotypes rather than just the one, and to include the most important capsular serotype for meningitis prevention (serotype 1). In addition we will test pneumococcal proteins that are found in higher quantities during meningitis to see whether they are effective vaccine candidates that can help prevent meningitis. The results of the work provide us with the necessary data on this vaccine approach for it to be developed and used in early phase clinical trials to demonstrate the vaccine is at least as good as the existing one.

Research activity codes: 3.4 VACCINES
Health categories: INFECTION