Deciphering the immune modulating roles of Staphylococcal Protein A (SpA) on the functional antibody response

Staphylococcus aureus is an opportunistic human pathogen causing diverse infection syndromes. Increasing concern regarding antibiotic resistance, and a lack of vaccines, underscores the need to understand the human immune response to invasive S. aureus to allow for new prevention strategies. Changes in B cell groups and antibody titres between infection states in relation to the infecting bacterial isolate were therefore investigated.

Adult participants with S. aureus bloodstream infections, other antimicrobial-resistant bacterial infections, and healthy controls were recruited from Sheffield Teaching Hospitals 7-14 days post infection confirmation. Bacterial isolates, plasma, and peripheral blood mononuclear cells (PBMC) were collected, with participants invited for a second visit 3-6 months post-infection. Bacterial isolates were sequenced to understand genomic differences, and an enzyme-linked immunosorbent assay (ELISA) assessed bacterial Staphylococcal protein A (SpA) production. The B cell repertoire was assessed via flow cytometry, and a multiplex bead assay investigated plasma IgG antibody titres and affinities against S. aureus antigens.

S. aureus were shown to possess diverse antibiotic resistance and virulence gene profiles. Heterogeneity in SpA secretion was observed which correlated with clonal complex. Flow cytometry analysis found there to be no expansion of key B cell populations at the point of infection. Antibody titres against key S. aureus antigens were heterogenous and not significantly different between healthy and infected individuals. Only SpA antibody titres both showed a significant increase when comparing bacteraemic and non-bacteraemic S. aureus infections, and a significant decrease in titre during convalescence. Antibody affinities showed no significant differences between clinical condition.

My findings highlight the complexity of S. aureus immunology, resulting in circulating antibody levels indistinguishable between healthy and infected individuals. The immune response to SpA appears to be altered in individuals with severe infections, suggesting that many antibodies are not induced by acute bloodstream S. aureus infection.