Current status

Project activities started with a Kick off meeting held in Siena on May 2014, when the criteria for the selection of the fellows have been discussed; the recruitment started in July 2014, when the call was published on several websites and the selection was concluded on September 2014. The Early Stage Researchers (ESR) selected for each position are:
ESR1: Maricarmen Rojas-López;
ESR2: Ricardo Jorge Rego Monteiro;
ESR3: Ilham Naili Rideout;
ESR4: Giulia Sagrestani.

The four fellows started between January and February 2015: ESR1 and ESR3 started at GSKVACSRL and moved to INRA after 19 months; ESR2 and ESR4 started at INRA and moved to GSKVACSRL after 17 months.

At GSKVACSRL Maricarmen Rojas-López, by a complementary approach exploiting both Reverse Vaccinology and molecular epidemiology tools, has identified new promising vaccine candidates that are expected to be able to induce protective functional antibodies against intestinal Escherichia coli (InPEC) strains. She is currently involved at INRA in the study of immunogenicity of few selected promising antigens in a mouse model.

Ricardo Monteiro started at INRA studying the cell surface and different cellular compartment proteome applying a Mass Spectrometry approach. Moreover he analysed the bacterial interaction with the host cells in order to better understand the level of expression of selected antigens during infection. In May 2016 Ricardo moved to GSK facilities in Siena (Italy) to integrate the Antigen Identification and Molecular Biology Unit. Here, Ricardo, is evaluating the potential adhesion characteristics of selected adhesins during Enterohaemorrhagic E. coli infection in intestinal cell models.

At GSK Vaccines Ilham Naili focused her research on the adaptive response, studying both cellular and serological key elements. She started investigating the response to a pathogenic Escherichia coli antigen previously identified at GSK Vaccines, and established a reproducible model of immunization using both mucosal and systemic routes that leads to a robust immune response, both at the intestinal level and systemically. She is currently investigating whether this specific immunization scheme leads to any perturbation of the intestinal microbiota, a key element to answer in the making of a vaccine against an intestinal pathogen. Ilham has started the second part of her doctoral program at INRA, where she is investigating the in vivo effect of nitric oxide on the fitness and survival of enterohaemorragic Escherichia coli using murine models of infection.

Giulia Sagrestani started at INRA studying the role that macrophages play in response to E. coli infection.
Giulia studied the effect of designated vaccine adjuvants on macrophage activation both, by in vitro and ex vivo models. In May 2016  Giulia joined GSK, with the aim to investigate  the effect of vaccine adjuvants on macrophage activation in vivo, in the mouse model.

All fellows participated to several training activities, both specific for their individual research projects, and on general and transferable skills, such as presentation skills, IP, legal, Grant proposal writing skills.
The fellows participated, and will participate in the future, in dissemination activities, presenting the results of their research to PhD workshops and scientific meetings.
Aiming to improve awareness of general public of the importance of preventive strategies against E. coli infections as an important way to improve quality of life and reduce the risk of life-threatening outbreaks from novel and uncontrolled hyper-virulent strains, the students are and will be involved in outreach activities.

Abstract

DISCo (A multidisciplinary Doctoral Industrial School on novel preventive strategies against E. Coli infections) is a doctoral school that originates from the common interest of GlaxoSmithKline Vaccines Srl (GSKVACSRL) and the French National Institute for Agronomical Research (INRA) in preventing E. coli infections. Both Institutes have a strong background in microbial pathogenesis, supported by a number of ongoing research programmes aimed at combating human infectious diseases. In particular, GSKVACSRL, by using a high-throughput in silico genomic approach, named “Reverse Vaccinology”, has recently delivered on the market Bexsero® that have been introduced in vaccination schedule in different Country for the prevention of meningococcal diseases. Starting from this successful achievement, we aim at applying both bioinformatic and experimental approaches (including proteomic, functional and immunological studies) to identify bacterial surface associated determinants able to induce cross-protective antibodies against different E. coli pathotypes. GSKVACSRL has already successfully exploited subtractive Reverse Vaccinology approach to identify novel immunogenic antigens capable of inducing protection against extraintestinal pathogenic E. coli species in a mouse model of sepsis. This doctoral program aims to extend such analysis to intestinal E. coli pathotypes for which a broadly protective vaccine is still not available but it would aid in the control of morbidity and mortality associated to diarrheal disease (especially in developing countries). Therefore, by combining the industrial expertise developed in GSKVACSRL with the academic research quality of INRA, we are implementing a strong training programme for young scientists who will have the unique opportunity to learn state-of-the art technologies jointly with the possibility of applying laboratory discoveries to industrial applications. The young fellows’ training path will be complemented by the transferable skills courses organized by the SME ALTA, and will culminate with the formal obtainment of the PhD title from two well recognized European universities, such as University of Roma 3 (Italy) and University of Auvergne (France).

 

 

 

This project has received funding from the People Programme (Marie Curie Actions)
of the European Union's Seventh Framework Programme FP7/2007-2013/ under REA grant agreement n° 607611