Staphylococcus aureus can cause severe life threatening invasive diseases. The principal immune effector mechanism by which humans are protected from Gram positive bacteria such as S. aureus is antigen specific antibody- and complement-dependent opsonophagocytosis. This process can be measured in vitro using the opsonophagocytic antibody assay (OPA), which is a complex assay composed of live S. aureus bacteria, a complement source, phagocytic effector cells such as differentiated HL-60 cells, and test serum. In this report, we investigated the impact on the OPA of S. aureus surface antigens capsular polysaccharides (CP) and protein A (SpA). We demonstrated that higher CP expression renders bacteria more resistant to non-specific opsonophagocytic killing than increased SpA expression, suggesting that the expression of capsular polysaccharides may be the more important immune evasion strategy for S. aureus. Bacteria that were not fully encapsulated were highly susceptible to non-specific killing in the assay in the absence of immune serum. This non-specific killing was prevented by growing the bacteria under conditions that increased capsular polysaccharide levels on the surface of the bacteria. In contrast, the level of SpA expression had no detectable effect on non-specific killing in OPA. Using anti-CP antibodies we demonstrated type-specific killing in OPA of both MRSA and MSSA clinical isolates. SpA expression on the cell surface did not interfere with OPA activity, providing evidence that despite the role of SpA in sequestering antibodies by their Fc region, killing is easily accomplished in the presence of high titered anti-capsular polysaccharide antibodies. This highlights the role of CP as an important immune evasion mechanism and supports the inclusion of capsular polysaccharide antigens in the formulation of multi-component prophylactic vaccines against S. aureus.

Staphylococcus aureus is a major cause of healthcare-associated infections and is responsible for a substantial burden of disease in hospitalized patients. Despite increasingly rigorous infection control guidelines, the prevalence and corresponding negative impact of S. aureus infections remain considerable. Difficulties in controlling S. aureus infections as well as the associated treatment costs are exacerbated by increasing rates of resistance to available antibiotics. Despite ongoing efforts over the past 20 years, no licensed S. aureus vaccine is currently available. However, learnings from past clinical failures of vaccine candidates and a better understanding of the immunopathology of S. aureus colonization and infection have aided in the design of new vaccine candidates based on multiple important bacterial pathogenesis mechanisms. This review outlines important considerations in designing a vaccine for the prevention of S. aureus disease in healthcare settings.

NCT01364571.