Broad and Effective Protection against Staphylococcus aureus Is Elicited by a Multivalent Vaccine Formulated with Novel Antigens

Abstract

The demand for a prophylactic vaccine against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) has motivated numerous dedicated research groups to design and develop such a vaccine. In this study, we have developed a multivalent vaccine, Sta-V5, composed of five conserved antigens involved in three important virulence mechanisms. This prototype vaccine conferred up to 100% protection against multiple epidemiologically relevant <i>S. aureus</i> isolates in five different murine disease models. The vaccine not only elicits functional antibodies that mediate opsonophagocytic killing of <i>S. aureus</i> but also mounts robust antigen-specific T-cell responses. In addition, our data implied that γδ T cells contribute to the protection induced by Sta-V5 in a murine skin infection model.<b>IMPORTANCE</b><i>Staphylococcus aureus</i> infections, especially MRSA infections, are becoming a major global health issue and are resulting in mortality rates that are increasing every year. However, an effective vaccine is lacking due to the complexity of the infection process of <i>S. aureus</i> In this study, we found that the addition of two novel protein components to three well-studied vaccine candidates significantly improved the efficacy of the combined vaccine. Furthermore, the five-component vaccine not only elicits a robust antibody response but also induces cytokine secretion by T cells, making it a promising vaccine candidate to fill the void.