Investigating the Immunogenic Potential of Flagella for Salmonella-Based Vaccine Carriers


Recombinant attenuated bacterial vector systems based on genetically engineered Salmonella Typhimurium have been developed as highly potent vaccines. These systems are able to trigger strong cellular and humoral immune responses against various pathogenic microorganisms and cancer. Due to the pathogenic nature of Salmonella, the bacteria need to be genetically modified to achieve an appropriate balance of attenuation and immune-stimulatory capacity. The flagellum is a major virulence factor of many pathogenic bacteria, including Salmonella. Flagella confers the ability to move in a directed manner towards and attach to host cells. In addition, the long external filament structure is a major pathogen-associated molecular pattern recognized by the mammalian immune system. Accordingly, Salmonella evolved sophisticated regulatory networks that ensure tight control of flagella synthesis during the course of infection. However, the role of the various regulatory factors and correct spatio-temporal synthesis of flagellar components during host-pathogen interactions remains elusive. We hypothesize that manipulating components of this regulatory network and the flagellar assembly pathway allows us to exploit the immunogenic potential of the flagellum for a generation of Salmonella vector strains exhibiting increased adjuvanticity. In this proof-of-concept study, we propose to construct various Salmonella mutants and test their immunogenicity in a mouse model for systemic infection with the aim to understand the regulatory interplay between the presence of flagella structures and the response of the immune system. In summary, the manipulation of flagella synthesis in directed strain design could represent a promising strategy to construct a potent bacterial vector system of the future. We thus believe that the findings of this study will allow us to generate an optimally balanced Salmonella vector strain to be used in a wide variety of vaccination and immunotherapy applications.


Principal Investigators
Erhardt, Marc Prof. Dr. (Details) (Bacterial Physiology)

Duration of Project
Start date: 01/2017
End date: 06/2018

Publications
1) Spöring, I. et al. Regulation of Flagellum Biosynthesis in Response to Cell Envelope Stress in Salmonella enterica Serovar Typhimurium. MBio 9, (2018).

2) Felgner, S. et al. The immunogenic potential of bacterial flagella for Salmonella‐mediated tumor therapy. International Journal of Cancer, (2019).

Last updated on 2021-11-10 at 11:58