Discovery of new immune response gives hope for new meningitis vaccine

12 Nov 2010

The discovery of a previously unknown immune response by scientists at the Universities of Leicester and Dublin has given a much needed breakthrough in the fight against pneumonia, meningitis and septicaemia.

The discovery will lead to a dramatic shift in our understanding of how the body’s immune system responds to infection caused by Streptococcus pneumoniae and could pave the way for more effective vaccines.

The two teams say they have shown for the first time that the bacterial toxin pneumolysin triggers an immune response by activating a recently discovered group of proteins, called the NLRP3 inflammasome. Once activated, the inflammasome provides protection against infection caused by Streptococcus pneumoniae.

They demonstrated that this mechanism operates independently of other previously described immune response proteins — contrary to current understanding in this field.

Importantly, this paper is the first to demonstrate that the NLRP3 inflammasome is essential to the immune response against infection by the pathogen and that the bacterial toxin pneumolysin is the key driver of this process.

The research was carried out by the teams from Leicester and Dublin with other collaborators from Trinity College Dublin, the US and Switzerland over four years and supported by Science Foundation Ireland, Enterprise Ireland, the UK Medical Research Council (MRC) and the Meningitis Research Foundation.

The research, which was jointly led by Dr Aras Kadioglu from the University of Leicester and Dr Ed Lavelle from Trinity College Dublin, with Dr Edel McNeela of TCD as its lead author, has been published in the journal PLoS Pathogens.

Dr Aras Kadioglu, Reader in Respiratory Infection in the Department of Infection, Immunity & Inflammation at the University of Leicester said: “This is a major breakthrough in our understanding of the immune response to Streptococcus pneumoniae; a human pathogen of global significance, responsible for over one million infant deaths annually and the major cause of illness and death in the elderly from infections of the respiratory tract.

"In order to develop improved pneumococcal vaccines for both the very young and the elderly, it is essential to understand how this bacterium interacts with the host immune system. The discoveries described in our paper represent a huge stride towards this objective. That is why these are exciting new findings, discovered in the course of a unique collaboration between scientists at the University of Leicester and Trinity College Dublin.”

Dr Lavelle, Lecturer in Immunology in the School of Biochemistry and Immunology, Trinity College Dublin, said: “This is a very exciting finding and supports the development of inflammasome activating vaccines to prevent pneumococcal diseases including pneumonia and septicaemia. If a protein-based vaccine could be produced that can protect against all strains of the pneumococcus, this would be of tremendous value and our discovery that NLRP3 is needed for protection will point us in the right direction in terms of how to develop such vaccines.”