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Abstract

Typhoid fever and non-typhoidal salmonelloses are responsible for a large disease burden worldwide and can coexist in the
same geographical area.
Vaccination remains the most feasible means to counteract Salmonella infections. Live attenuated vaccines induce both
antibody and protective Th1 responses that are essential to control bacteraemia during a secondary challenge and restrain
growth and inter-organ spread of the bacteria in the systemic organs.
One of the concerns over the use of live vaccines is their potential residual virulence, especially in areas of the world where
comorbidities and immunodeficiences are prevalent and in many cases undiagnosed.
We have therefore searched for Salmonella genes that can be deleted to generate live attenuated vaccines with increased safety
in situations where the immune system is impaired. We have used a global approach based on Transposon Directed Insertionsite
Sequencing (TraDIS) to gain a numerical measure of the extent to which mutants are negatively or positively selected
during infection in wild-type mice and in gene-targeted mice representative of common immunodeficiencies that predispose
to salmonelloses. We have identified gene candidates that can be deleted to construct live vaccines with reduced and/or delayed
reactogenicity in immunodeficient hosts. One of these vaccine strains has been further tested in immunocompromised mice
and has shown increased safety as measured by delayed appearance of signs of infection in comparison with other established
single mutant vaccine candidates. This mutant colonises mice via the oral and parenteral route and confers protection against
lethal oral challenge with virulent Salmonella.

Biography

Pietro Mastroeni received Degree in Medicine and Surgery from the University of Messina, Italy. He moved to the University of Cambridge, UK where he completed
his Ph.D. before becoming a Research Fellow at Imperial College, University of London UK. He is currently a Reader in Infection and Immunity at the University of
Cambridge. He has published more than 100 papers in reputed journals and served as an editorial board member.