Rapid and Broad Immune Efficacy of a Recombinant Five-Antigen Vaccine Against <i>Staphylococcus aureus</i> Infection in Animal Models

Abstract

Staphylococcus aureus (S.aureus) is a leading cause of both healthcare-and community-associated infections globally, which result in severe disease and readily developing antibiotic resistance. So developing an efficacious vaccine against S.aureus is urgently required. In the present study, we selected five conserved antigens, which were all well-characterized virulence factor of S. aureus by using a reverse vaccine strategy and developed a recombinant five-antigen S. aureus vaccine (rFSAV). Including the secreted factors α-hemolysin (Hla), staphylococcal enterotoxin B (SEB), and the three surface proteins staphylococcal protein A (SpA), iron surface determinant B N2 domain (IsdB-N2) and manganese transport protein C (MntC). rFSAV provided consistent protection in S. Aureus lethal sepsis, pneumonia and fracture fixation mouse models, and it showed broad immune protection when challenged with a panel of epidemiologically relevant S.aureus strains. Meanwhile, rFSAV immunized mice with an optimal immunization procedure (days 0, 3, and 7) were able to induce comprehensive cellular and humoral immune responses to reduce bacterial loads, inflammatory cytokine expression, inflammatory cell infiltration and decrease pathology after challenge with a sub-lethal dose of S. aureus. Moreover, the importance of specific antibodies in protection was demonstrated by passive transfer experiments. Altogether, our data demonstrate that rFSAV is a potentially promising vaccine candidate for defensing against S. aureus infection. Funding Statement: This work was supported by the National Natural Science Foundation of China [grant number 81172892 and 31370932] and the key project of innovative drug development [grant number 2015ZX09101033 and 2016ZX09J16102-002]. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: All animal care and use protocols in this study were performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People's Republic of China. All animal experiments in this study were approved by the Animal Ethical and Experimental Committee of the Third Military Medical University (Chongqing, Permit No. 2011- 04) in accordance with their rules and regulations.