A multivalent mRNA-LNP cocktail vaccine confers superior efficacy against Staphylococcus aureus infection in murine models
Xingyue Gao, Yueling Zheng, Xingyun Wang, Jiahui Jin, Cong Liu, Chuanlan Yang, Peng George Wang, Yunjiao He
Abstract
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.