Staphylococcus aureus (SA), a human commensal bacteria, is a significant cause of skin/soft tissue infections, surgical site infections, and bacteremia. Protection is considered to be mediated by functional antibodies and T-cell-mediated immunity, particularly Th1/Th17 responses. Vaccine development may be hampered by pathogen-activated immunoregulatory responses, such as IL-10, which modulate vaccine-induced T cells. Using healthy donor-derived PBMCs, researchers tested SA proteins for CD4+ T-cell activation and IL-10/IL-17 induction. Th1/Th17 cell phenotypic plasticity was assessed utilizing modulatory cytokines under pro- or anti-inflammatory settings. Vaccination’s effect on SA-specific memory responses was studied using samples from a clinical study comparing AS03-adjuvanted and non-adjuvanted multicomponent vaccinations. SA-specific memory T-cell responses were seen in the donors, indicating pre-existing immunity to SA. We discovered efficient activators of Th1 responses, Th17 and Th1/Th17 responses, but not Th22 or IL-10 production. In the tests, MRPII, IsdA, and ClfA were ineffective CD4+ T-cell activators. Memory CD4+ T-cells detected following long-term stimulation with -toxin and ClfA suggested that immunization with these proteins caused amplification of pre-existing Th1 but not Th17 responses, with no apparent adjuvant impact, corroborating trial findings. Under pro- and anti-inflammatory circumstances, the Th1/Th17-driving proteins shared poor IL-10-promoting capacities and limited phenotypic plasticity. 

Given the complexities of immunopathology and numerous virulence variables, identifying Th1/Th17-driving antigens, adjuvants, and delivery methods, as well as delineating the involvement of memory responses, may help to enhance vaccine development.