Protective Efficacy and Mechanism of Passive Immunization with Polyclonal Antibodies in a Sepsis Model of Staphylococcus aureus Infection.

Staphylococcus aureus (S. aureus) is an opportunistic bacterial pathogen responsible for a diverse spectrum of human diseases, resulting in considerable yearly mortality rates. Due to its rapid acquisition of antibiotic resistance, it becomes increasingly difficult to cure S. aureus infections with conventional antibiotics. Immunotherapy represents a promising alternative strategy to prevent and/or treat the infection. In the present study, passive immunization with polyclonal antibodies targeting three possible S. aureus antigens, Hla, SEB and MntC (termed "SAvac-pcAb") after challenge with lethal dose of S. aureus resulted in reduced bacterial loads, inflammatory cell infiltration and decreased pathology, and was able to provide nearly complete protection in a murine sepsis model. In vitro studies confirmed the direct interaction of SAvac-pcAb with S. aureus bacteria. Additional studies validated that SAvac-pcAb contained both opsonic and neutralizing antibodies that contributed to its protective efficacy. The former mediated opsonophagocytosis in a neutrophil-dependent manner, while the later inhibited the biological functions of Hla and SEB, two major virulence factors secreted by S. aureus. Critically, we demonstrated that SAvac-pcAb was cross-reactive with different clinical strains of S. aureus. These results confirmed the efficacy for treatment of S. aureus infection by passive immunization as an important therapeutic option.

Evaluation of the protective immunity of a novel subunit fusion vaccine in a murine model of systemic MRSA infection.

Staphylococcus aureus is a common commensal organism in humans and a major cause of bacteremia and hospital acquired infection. Because of the spread of strains resistant to antibiotics, these infections are becoming more difficult to treat. Therefore, exploration of anti-staphylococcal vaccines is currently a high priority. Iron surface determinant B (IsdB) is an iron-regulated cell wall-anchored surface protein of S. aureus. Alpha-toxin (Hla) is a secreted cytolytic pore-forming toxin. Previous studies reported that immunization with IsdB or Hla protected animals against S. aureus infection. To develop a broadly protective vaccine, we constructed chimeric vaccines based on IsdB and Hla. Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses. When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla). Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.

Helicobacter pylori chaperone-like protein CagT plays an essential role in the translocation of CagA into host cells.

Most of the Helicobacter pylori strains containing the cag pathogenicity island (PAI) have been associated with more severe gastric disease in infected humans. The cag PAI is composed of 27 proteins, and some of the components are required for CagA translocation into host cells as well as induction of proinflammatory cytokines, such as interleukin-8 (IL-8); however, the exact function of most of the components remains unknown or poorly characterized. In this study, we demonstrated that CagT (HP0532), which is an essential structural component of the cag PAI apparatus, plays an important role in the translocation of CagA into host epithelial cells. In addition to being located on the bacterial surface, CagT is also partially localized in the inner membrane, where it acts as a chaperone-like protein and promotes CagA translocation. However, CagT secretion was not detected by immunoprecipitation analysis of cell culture supernatants. Meanwhile, CagT was related to the introduction of IL-8 of the host cell. These results suggest that CagT is expressed on both the inner and outer bacterial membranes, where it serves as a unique type IV secretion system component that is involved in CagA secretion and cag PAI apparatus assembly.