Safety, Efficacy, and Immunogenicity of a Multivalent Adjuvanted Staphylococcus aureus Vaccine in Adults With Recent Skin and Soft Tissue Infections: An Observer-Blind, Randomized, Placebo-Controlled, Multinational Phase 1/2 Trial

Abstract Background A vaccine that prevents Staphylococcus aureus skin and soft tissue infections (SA-SSTIs) would have a major impact on public health. Methods A 2-part randomized study began with a phase 1, first-in-human, dose escalation that tested the safety of the 5-antigen S. aureus vaccine (SA5Ag), half or full antigen doses, unadjuvanted or with AS01E adjuvant, in 32 healthy volunteers aged 18–50 years. In the phase 2, proof-of-principle part, 194 participants aged 18–64 years with recent SA-SSTI were administered 2 full doses of AS01E-adjuvanted SA5Ag (SA5Ag-Adj) or placebo, 2 months apart, and followed for 12 months. Vaccine safety (primary objective), vaccine efficacy (VE; secondary/tertiary objectives), and immunogenicity (tertiary objectives) were evaluated. Results Following a positive safety evaluation in phase 1, participants were enrolled into phase 2 until predefined futility criteria were met at the interim efficacy analysis. Twelve months post-dose 2, SA5Ag-Adj showed no efficacy in preventing recurrent SA-SSTIs (VE, −38.1%; 95% confidence interval, −245.8 to 40.9), despite inducing robust functional immune responses against 3 (S. aureus capsular polysaccharide types 5 and 8 [CP5 and CP8], alpha-hemolysin [Hla]) of the 5 vaccine antigens. Solicited local adverse events (AEs) were more frequent in the SA5Ag-Adj group versus the placebo group but were mostly mild or moderate in intensity. Frequencies of medically attended AEs and serious AEs were similar across groups. Conclusions In participants with recent history of SA-SSTI, SA5Ag-Adj vaccine had an acceptable safety profile and induced robust functional immune responses against CP5, CP8, and Hla antigens but did not reduce the rate of recurrent SA-SSTIs at 12 months from last dose. Clinical Trial Registration. NCT04420221.