A multivalent porin mRNA vaccine against diseases caused by Salmonella

Summary 

Infections caused by Salmonella represent a major public health problem globally, even more so with the raise in antimicrobial resistance. In this project we take advantage of mRNA vaccine technology to test several vaccine candidates based on Salmonella porins. The vaccine protection will be evaluated in mice challenged with different Salmonella serovars.

We aim to obtain proof-of-concept evidence that a multivalent Salmonella mRNA vaccine could provide cross protection against endemic, typhoid and non typhoid strains that cause systemic and gastrointestinal manifestations.

Project Outcomes

We successfully designed and synthesized mRNA constructs encoding the Salmonella proteins OmpC, OmpF, and OmpD. These constructs were efficiently translated in an in vitro system, expressed in Huh-7 cells, and recognized by antigen-specific antibodies generated against purified Salmonella proteins.Immunogenicity assessment of the OmpD mRNA construct revealed no detectable antibody responses, prompting the need for further evaluation of antigen-specific T cell responses. In initial challenge studies using a model primarily reliant on antibody-mediated protection, no significant protection against infection was observed. However, in an intragastric challenge model extending over 10 days, we noted a higher percentage of survival in mRNA-immunized mice, although this difference did not reach statistical significance. These findings suggest the need for further optimization and investigation of the immune mechanisms elicited by the mRNA constructs.