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. Developing an efficacious vaccine against S. aureus is urgently required. In the present study, we selected five conserved antigens, 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). They were all well-characterized virulence factor of S. aureus and developed a recombinant five-antigen S. aureus vaccine (rFSAV), rFSAV provided consistent protection in S. aureus lethal sepsis and pneumonia mouse models, and it showed broad immune protection when challenged with a panel of epidemiologically relevant S. aureus strains. Meanwhile, rFSAV immunized mice 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 antibody function tests in vitro and in vivo. Altogether, our data demonstrate that rFSAV is a potentially promising vaccine candidate for defensing against S. aureus infection.
Highlights
Staphylococcus aureus (S. aureus) is an important pathogen that causes hospital and community infections, such as sepsis, pneumonia, infective endocarditis, septic arthritis, fracture fixation and invasive infections, and its mortality rate is up to 20% [1]
100 μL of wild type staphylococcal protein A (SpA) (SpA, 1.5 mg/mL) that had been incubated with 2 mg of recombinant five-antigen S. aureus vaccine (rFSAV)-pcAb or negative-pcAb 30 min prior to the start of the study was injected into the peritoneum of six-week-old female BALB/c mice
The results showed that the bacterial burden in the blood, kidneys and spleen was much lower in the rFSAV group than the AlPO4 control group at 1 day post-infection (p blood = 0.0033, p kidney = 0.0004 and p spleen = 0.0101, Figure 2A)
Summary
Staphylococcus aureus (S. aureus) is an important pathogen that causes hospital and community infections, such as sepsis, pneumonia, infective endocarditis, septic arthritis, fracture fixation and invasive infections, and its mortality rate is up to 20% [1]. Our vaccine contains five antigen targets, including SpA, Hla, IsdB-N2, SEB and MntC. These antigens contain bacterial toxin molecules, membrane proteins and proteins closely associated with bacterial growth metabolism. The vaccine using these proteins as antigens offers enhanced protection by inhibiting or blocking key pathogenic links, such as bacterial adhesion, toxin release, metabolism and immune escape. Our vaccine works by multiple immunologic mechanisms, and induced robust antigen specific humoral and cellular immune response, obviously producing immuno-protection against different sources of S. aureus strain infections in animal models of systemic infection and pulmonary infection
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