Kick-starting production process development of a porin-based NTS vaccine: Strain selection

Summary

Development of a vaccine against Non Typhoidal Salmonellosis remains an unmet public health need. Purified outer membrane proteins (porins) from Salmonella Typhimurium (STm) have been highlighted as promising vaccine candidates. Our research team has the ability to produce highly purified porins, however the process uses a commercial strain that would complicate further development. On the other hand we have a large collection of STm strains that could be used as producing strains. In this project we aim to explore our strain collection and characterise porin producing strains that could be used in our production process. Furthermore we will purify porins from the selected strains and test their ability to trigger bactericidal antibodies against non-MDR and MDR STm strains.

Project Outcomes

STm porins represent promising vaccine candidates against NTS.  Our team is currently developing a scaled-up production process in order to be able to manufacture this vaccine candidate at an industrial scale. As part of this scale-up process, selection of a suitable producing strain is critical. In this work we selected two strains from a panel of STm clinical isolates, representative of the ST213 genotype firstly reported in Mexico. Two novel STm strains were successfully used for STm porin production and the purified products were mainly composed of OmpC and OmpD, as shown by LC-MS analysis. One strain in particular had a significantly high yield of purified protein and low levels of LPS in the final product. The purified porins were highly immunogenic in mice, even in the absence of adjuvants, and antibody titres were higher in those mice immunised with porins purified from the novel strains compared to our reference strain. Studies regarding the protective efficacy of these porin preparations are still underway and will be critical to push forward the use of either one of this STm strains.