mRNA based vaccine approach against Salmonella infection

Summary 

Salmonella enterica is a leading cause of food poisoning and typhoid disease. Compounding this issue is the emergence of multi-drug resistant strains, posing grave risks to human health. Combatting the escalating threat of antibiotic resistance necessitates novel intervention methods, notably vaccines. Yet, existing Salmonella vaccines offer only fleeting protection against typhoid fever and lack efficacy in safeguarding young individuals. Previously, our research pinpointed a set of four highly conserved Salmonella antigens. We demonstrated that immunization with these antigens conferred protection in a murine model against lethal Salmonella challenges. Notably, our findings extended to providing defence against heterologous challenges with distinct serovars. Fuelled by the COVID-19 pandemic, mRNA vaccines have emerged as potent alternatives to conventional protein subunit vaccines. Their attributes include heightened potency, safety, efficacy, rapid clinical development, and potential for cost-effective manufacturing. Building upon this momentum, we hypothesize that harnessing mRNA technology will serve to complement and potentially enhance the outcomes achieved thus far in Salmonella vaccine development. Here we will benchmark mRNA versions of our vaccine components against the protein vaccines, establishing if they are effective at reducing bacterial loads in an acute model of infection, and if they prolong survival against a lethal challenge.

Project Outcomes

Salmonella enterica infects a broad range of hosts and is a leading cause of food poisoning and typhoid diseases. The rise of antibiotic-resistant Salmonella strains has restricted treatment options. There is an urgent need for a vaccine that provides long lasting protection against all strains of Salmonella. We have previously identified four highly conserved antigens in Salmonella and demonstrated that immunisation with these antigens induces robust antibody responses and provides protection against lethal challenges with distinct serovars of Salmonella. mRNA vaccine delivery systems present a promising alternative to conventional protein-based vaccines. Here, we benchmarked mRNA sequences encoding the four Salmonella antigens against the protein vaccines. The mRNA versions of our vaccines elicited antibody responses in mice which were comparable to the protein-based vaccine; however, they did not provide similar protective efficacy at early time points of infection. Furthermore, in the survival assay, the mRNA vaccines alone exhibited similar mortality rates to the non-immunised group. Although, combining the mRNA vaccines with OMVs extended survival in mice, the four antigen protein-based vaccines outperformed all other groups.