Immune Defects of Invasive Pneumococcal Diseases
Research type
Research Study
Full title
Detection of subtle immune defects in individuals at risk of invasive pneumococcal disease
IRAS ID
153987
Contact name
Thushan De Silva
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 8 months, 30 days
Research summary
Research Summary:
Invasive infections caused by Streptococcus pneumoniae (Invasive Pneumococcal Disease, IPD) such as pneumonia with bloodstream infection and meningitis still continue to occur despite the availability of two vaccines against this organism. While these are more common in those with risk factors which affect the immune system (e.g. HIV), a proportion of individuals with no apparent immunological problem also suffer from IPD. We have previously shown the presence of a subtle problem in the immune systems of these individuals, where their B-cells (the main cell type that produces antibodies, which in turn is a major component of the body's defense against Streptococcus pneumoniae and are usually enhanced by vaccines) are not activated as well as individuals who do not have a history of IPD. We propose to extend these findings by exploring the mechanism behind this defect. This will be done by performing laboratory experiments measuring differences in gene expression between subjects who have a history of IPD and healthy controls after their B-cells are stimulated. We also propose to see whether other groups of individuals who either have a history of IPD or are at risk of IPD have similar defects in their B-cell activation or if there are different mechanisms for the increased susceptibility to Streptococcus pneumoniae: 1. Subjects with a history of IPD but have been vaccinated with the polysaccharide pneumococcal vaccine previously (ie vaccine failures), subjects with HIV on antiretroviral therapy with high CD4 counts (these individuals still remain susceptible) and subjects with a range of haematological conditions affecting B-cells.Lay summary of study results:
This study looked at a particular part of our body’s defences against bugs that cause pneumonia (B cells) and whether there are weaknesses in this aspect in people living with HIV. We used blood from volunteers and tested how their B cells worked in the laboratory using a response to something similar to a pneumonia vaccine. We found that in people living with HIV who are well and on HIV medication, their B cells worked very similarly to people without HIV.REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
14/YH/1118
Date of REC Opinion
21 Oct 2014
REC opinion
Further Information Favourable Opinion