The bacterium Escherichia coli normally inhabits our intestines but when it occurs in body sites outside the intestines, it can cause serious diseases. These extraintestinal pathogenic Escherichia coli (ExPEC) are important causes of morbidity and mortality, worldwide, being the number one cause of urinary tract infections and being the second most frequent cause of meningitis and sepsis in neonates. The extent of these infectious diseases plus the increasing occurrence of antibiotic resistance ExPEC means that possession of an effective vaccine is a public health priority. Unfortunately, effective protective vaccines against ExPEC are not available at present. This joint project of the University of Leicester with GSK Vaccines aims to make an important contribution to the solution of this deficiency. One of the hurdles in vaccine development is the difficulty in doing large scale vaccine efficacy tests in animals or humans. An excepted means to overcome this issue is to use straightforward in vitro tests that reflect and predict efficacy in vivo, in other words are correlates of protection. Sadly, in the case of ExPEC, the classical opsonophagocytic or bactericidal assays do not give correlates of protection, raising the need for novel tests to prioritise vaccine antigens during preclinical screening. We have recently discovered that bacterial replication within splenic macrophages precedes and correlates to invasive sepsis disease. Using samples of spleens in culture, in this project we will test if prevention this splenic phase of ExPEC infection is a correlate of protection and can be used for vaccine antigen screening.
Our research hypothesis was that we would be able to detect significantly different bacterial organ counts in early infection stage animals few hours after the challenge in mice vaccinated with protective antigens, both by passive or active immunization. The different counts were then to be traced back to differences in interaction of the bacteria with tissue macrophages.
The experiments provide a clear response to our hypothesis. Unfortunately, for our research perspective, our initial hypothesis was not supported by the data.
Professor Marco Rinaldo Oggioni
Dept. Genetics and Genome Biology, University of Leicester (UK)
Dr Mariagrazia Pizza, GSK Vaccines (Italy)
Professor Peter W Andrew, Dept. Respiratory Science, University of Leicester (UK)