Safety, Efficacy, and Immunogenicity of a Multivalent Adjuvanted S. aureus Vaccine in Adults with Recent Skin And Soft Tissue Infections: An Observer-blind, Randomized, Placebo-controlled, Multinational Phase 1/2 Trial.

Abstract

A vaccine that prevents Staphylococcus aureus skin and soft tissue infections (SA-SSTIs) would have a major impact on public health. A two-part randomized study began with a phase 1, first-in-human, dose-escalation that tested the safety of the five-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 two 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. 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, 40.9]), despite inducing robust functional immune responses against three (CP5, CP8, Hla) of the five vaccine antigens. Solicited local adverse events (AEs) were more frequent in the SA5Ag-Adj versus placebo group but were mostly mild or moderate in intensity. Frequencies of medically-attended AEs and serious AEs were similar across groups. In participants with recent history of SA-SSTI, SA5Ag-Adj vaccine had an acceptable safety profile, 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. NCT04420221.