A multivalent mRNA-LNP cocktail vaccine confers superior efficacy against Staphylococcus aureus infection in murine models

Staphylococcus aureus has been posing a significant global health threat, underscoring an urgent need for innovative preventive strategies, notably vaccines. This study presents an evaluation of a multi-target mRNA vaccine against S. aureus, engineered to target five pivotal virulence factors: the manganese transporter MntC, enterotoxin SEB, exotoxin HLA, adhesion factor FnBPA, and iron surface binding protein IsdB. In a parallel control setting, mice were immunized with either monovalent mRNA-LNPs, a multivalent mRNA-LNP cocktail, or a protein cocktail, and were subsequently assessed for humoral and cellular immune responses as well as the vaccines' protective efficacy. The findings demonstrated that the multivalent mRNA-LNP cocktail vaccine induced a robust and sustained humoral immune response, along with a stronger cellular immune response compared to both monovalent mRNA vaccines and the protein cocktail vaccine. This was characterized by increased secretion of IFN-γ, IL-2, IL-4, and IL-17A, suggesting a potent Th1/Th2/Th17 mixed immune response. Moreover, the cocktail vaccine demonstrated improved survival rates and a reduction in bacterial loads and organ damage. These results underscore the promise of a multi-target mRNA vaccine strategy in combating antibiotic-resistant Staphylococcus aureus.